SEC Info℠  
    Home      Search      My Interests      Help      Sign In      Please Sign In

Opko Health, Inc. – ‘10-K’ for 12/31/20 – ‘EX-101.DEF’

On:  Thursday, 2/18/21, at 4:09pm ET   ·   For:  12/31/20   ·   Accession #:  944809-21-15   ·   File #:  1-33528

Previous ‘10-K’:  ‘10-K’ on 3/2/20 for 12/31/19   ·   Next:  ‘10-K’ on 3/1/22 for 12/31/21   ·   Latest:  ‘10-K’ on 3/1/24 for 12/31/23   ·   50 References:   

Find Words in Filings emoji
 		  in    Show  and   ↓Hints

  As Of               Filer                 Filing    For·On·As Docs:Size

 2/18/21  Opko Health, Inc.                 10-K       12/31/20  111:16M

Annual Report   —   Form 10-K
Filing Table of Contents

Document/Exhibit                   Description                      Pages   Size 

 1: 10-K        Annual Report                                       HTML   2.05M 
 2: EX-3.2      Articles of Incorporation/Organization or Bylaws    HTML    104K 
 3: EX-4.6      Instrument Defining the Rights of Security Holders  HTML     38K 
 4: EX-21       Subsidiaries List                                   HTML     32K 
 5: EX-23.1     Consent of Expert or Counsel                        HTML     30K 
 6: EX-31.1     Certification -- §302 - SOA'02                      HTML     33K 
 7: EX-31.2     Certification -- §302 - SOA'02                      HTML     33K 
 8: EX-32.1     Certification -- §906 - SOA'02                      HTML     29K 
 9: EX-32.2     Certification -- §906 - SOA'02                      HTML     29K 
16: R1          Cover Page                                          HTML     90K 
17: R2          Consolidated Balance Sheets                         HTML    121K 
18: R3          Consolidated Balance Sheets (Parenthetical)         HTML     37K 
19: R4          Consolidated Statements of Operations               HTML    102K 
20: R5          Consolidated Statements of Comprehensive Income     HTML     49K 
                (Loss)                                                           
21: R6          Consolidated Statements of Equity                   HTML     95K 
22: R7          Consolidated Statements of Cash Flows               HTML    139K 
23: R8          Business and Organization                           HTML     34K 
24: R9          Impact of COVID-19                                  HTML     38K 
25: R10         Summary of Significant Accounting Policies          HTML     69K 
26: R11         Income (loss) Per Share                             HTML     34K 
27: R12         Investments                                         HTML     62K 
28: R13         Composition of Certain Financial Statement          HTML    166K 
                Captions                                                         
29: R14         Debt                                                HTML    111K 
30: R15         Shareholders' Equity                                HTML     36K 
31: R16         Accumulated Other Comprehensive Income (Loss)       HTML     41K 
32: R17         Equity-Based Compensation                           HTML     61K 
33: R18         Income Taxes                                        HTML    140K 
34: R19         Related Party Transactions                          HTML     44K 
35: R20         Employee Benefit Plans                              HTML     34K 
36: R21         Commitments and Contingencies                       HTML     43K 
37: R22         Revenue Recognition                                 HTML    117K 
38: R23         Strategic Alliances                                 HTML     50K 
39: R24         Leases                                              HTML    112K 
40: R25         Segments                                            HTML    112K 
41: R26         Fair Value Measurements                             HTML     93K 
42: R27         Derivative Contracts                                HTML     49K 
43: R28         Selected Quarterly Financial Data (Unaudited)       HTML     54K 
44: R29         Subsequent Events                                   HTML     31K 
45: R30         Summary of Significant Accounting Policies          HTML    125K 
                (Policies)                                                       
46: R31         Investments (Tables)                                HTML     55K 
47: R32         Composition of Certain Financial Statement          HTML    167K 
                Captions (Tables)                                                
48: R33         Debt (Tables)                                       HTML     98K 
49: R34         Accumulated Other Comprehensive Income (Loss)       HTML     40K 
                (Tables)                                                         
50: R35         Equity-Based Compensation (Tables)                  HTML     57K 
51: R36         Income Taxes (Tables)                               HTML    136K 
52: R37         Revenue Recognition (Tables)                        HTML     95K 
53: R38         Leases (Tables)                                     HTML     85K 
54: R39         Segments (Tables)                                   HTML    110K 
55: R40         Fair Value Measurements (Tables)                    HTML     93K 
56: R41         Derivative Contracts (Tables)                       HTML     51K 
57: R42         Selected Quarterly Financial Data (Unaudited)       HTML     54K 
                (Tables)                                                         
58: R43         Business and Organization - Narrative (Details)     HTML     30K 
59: R44         Impact of COVID-19 (Details)                        HTML     41K 
60: R45         Summary of Significant Accounting Policies -        HTML    130K 
                Narrative (Details)                                              
61: R46         Income (loss) Per Share - Narrative (Details)       HTML     41K 
62: R47         Investments - Accounting Method, Carrying Value     HTML     44K 
                and Underlying Equity in Net Assets of                           
                Unconsolidated Investments (Details)                             
63: R48         Investments - Narrative (Details)                   HTML    111K 
64: R49         Investments - Schedule of Net Gains and Losses on   HTML     36K 
                Equity Securities (Details)                                      
65: R50         Composition of Certain Financial Statement          HTML    166K 
                Captions - Composition of Certain Financial                      
                Statement Captions (Details)                                     
66: R51         Composition of Certain Financial Statement          HTML     64K 
                Captions - Narrative (Details)                                   
67: R52         Composition of Certain Financial Statement          HTML     44K 
                Captions - Summary of Valuation Allowance                        
                (Details)                                                        
68: R53         Composition of Certain Financial Statement          HTML     80K 
                Captions - Changes in Goodwill (Details)                         
69: R54         Debt - Schedule of Debt (Details)                   HTML     59K 
70: R55         Debt - Narrative (Details)                          HTML    224K 
71: R56         Debt - Schedule of Notes (Details)                  HTML     56K 
72: R57         Debt - Summary of Lines of Credit (Details)         HTML     72K 
73: R58         Debt - Mortgage Notes and Other Debt (Details)      HTML     38K 
74: R59         Shareholders' Equity - Narrative (Details)          HTML     80K 
75: R60         Accumulated Other Comprehensive Income (Loss) -     HTML     39K 
                Changes in Accumulated Other Comprehensive Income,               
                Net of Tax (Details)                                             
76: R61         Equity-Based Compensation - Narrative (Details)     HTML     77K 
77: R62         Equity-Based Compensation - Summary of              HTML     47K 
                Option-Pricing Formula (Details)                                 
78: R63         Equity-Based Compensation - Summary of Option       HTML     80K 
                Activity (Details)                                               
79: R64         Income Taxes - Components of Income Tax Benefit     HTML     57K 
                (Provision) (Details)                                            
80: R65         Income Taxes - Components of Deferred Income Tax    HTML     89K 
                Assets and Liabilities (Details)                                 
81: R66         Income Taxes - Narrative (Details)                  HTML     61K 
82: R67         Income Taxes - Change in Gross Unrecognized Income  HTML     41K 
                (Details)                                                        
83: R68         Income Taxes - Schedule of Difference in Federal    HTML     67K 
                and Effective Tax Rate (Details)                                 
84: R69         Income Taxes - Reconciliation Losses Before Tax,    HTML     36K 
                US and Foreign Jurisdictions (Details)                           
85: R70         Related Party Transactions - Narrative (Details)    HTML    262K 
86: R71         Employee Benefit Plans - Narrative (Details)        HTML     38K 
87: R72         Commitments and Contingencies - Narrative           HTML     62K 
                (Details)                                                        
88: R73         Revenue Recognition - Narrative (Details)           HTML     65K 
89: R74         Revenue Recognition - Schedule of Disaggregation    HTML     50K 
                of Revenue (Details)                                             
90: R75         Revenue Recognition - Schedule of Product Sales     HTML     65K 
                Allowances and Accruals (Details)                                
91: R76         Revenue Recognition - Changes in Contractual        HTML     33K 
                Liabilities Balance (Details)                                    
92: R77         Strategic Alliances - Narrative (Details)           HTML    133K 
93: R78         Leases - Lease Assets and Liabilities (Details)     HTML     59K 
94: R79         Leases - Lease Liability Maturity (Details)         HTML     69K 
95: R80         Leases - Narrative (Details)                        HTML     35K 
96: R81         Leases - Supplemental Cash Flow Information         HTML     37K 
                (Details)                                                        
97: R82         Segments - Narrative (Details)                      HTML     41K 
98: R83         Segments - Operations and Assets for Operating      HTML    125K 
                Segments and Geographic Information (Details)                    
99: R84         Segments - Property, Plant and Equipment, Net by    HTML     36K 
                Jurisdiction (Details)                                           
100: R85         Fair Value Measurements - Financial Assets and      HTML     66K  
                Liabilities Measured at Fair Value on a Recurring                
                Basis (Details)                                                  
101: R86         Fair Value Measurements - Carrying Amount and       HTML     40K  
                Estimated Fair Value of Long-Term Debt (Details)                 
102: R87         Fair Value Measurements - Reconciliation of         HTML     35K  
                Beginning and Ending Balances of Level 3 Assets                  
                and Liabilities (Details)                                        
103: R88         Fair Value Measurements - Narrative (Details)       HTML     36K  
104: R89         Derivative Contracts - Summary of Fair Values and   HTML     42K  
                Presentation of Derivative Financial Instruments                 
                (Details)                                                        
105: R90         Derivative Contracts - Summary of the Losses and    HTML     37K  
                Gains Recorded for the Changes in Fair Values of                 
                Derivative Instruments (Details)                                 
106: R91         Selected Quarterly Financial Data (Unaudited) -     HTML     49K  
                Summary of Selected Quarterly Financial Data                     
                (Unaudited) (Details)                                            
107: R9999       Uncategorized Items - opk-20201231.htm              HTML     37K  
109: XML         IDEA XML File -- Filing Summary                      XML    198K  
15: XML         XBRL Instance -- opk-20201231_htm                    XML   4.10M 
108: EXCEL       IDEA Workbook of Financial Reports                  XLSX    173K  
11: EX-101.CAL  XBRL Calculations -- opk-20201231_cal                XML    356K 
12: EX-101.DEF  XBRL Definitions -- opk-20201231_def                 XML   1.29M 
13: EX-101.LAB  XBRL Labels -- opk-20201231_lab                      XML   2.87M 
14: EX-101.PRE  XBRL Presentations -- opk-20201231_pre               XML   1.76M 
10: EX-101.SCH  XBRL Schema -- opk-20201231                          XSD    261K 
110: JSON        XBRL Instance as JSON Data -- MetaLinks              625±   907K  
111: ZIP         XBRL Zipped Folder -- 0000944809-21-000015-xbrl      Zip    704K

‘EX-101.DEF’   —   XBRL Definitions — opk-20201231_def

This Exhibit is an XBRL XML File.

                                                                                                                                                                                
<?xml version="1.0" encoding="windows-1252"?>
<!-- XBRL Document Created with Wdesk from Workiva -->
<!-- Copyright 2021 Workiva -->
<!-- r:0cdcc711-982e-4bc8-9796-0571c76897bd,g:f9be14b8-63fe-4945-add1-8a989ed6e22b -->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
<link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
<link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
<link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
<link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
<link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
<link:roleRef roleURI="http://www.opko.com/role/COVERPAGE" xlink:type="simple" xlink:href="opk-20201231.xsd#COVERPAGE"/>
<link:definitionLink xlink:role="http://www.opko.com/role/COVERPAGE" xlink:type="extended" id="i5a40466af7964bacac1ea4d134e8efe2_COVERPAGE"/>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedBalanceSheets" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedBalanceSheets"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedBalanceSheets" xlink:type="extended" id="i50aa0d88e464450e96925ab125bd3cfc_ConsolidatedBalanceSheets"/>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedBalanceSheetsParenthetical"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedBalanceSheetsParenthetical" xlink:type="extended" id="ibce3d6ed4bbc4085a533852bc592e8c7_ConsolidatedBalanceSheetsParenthetical"/>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedStatementsofOperations" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedStatementsofOperations"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedStatementsofOperations" xlink:type="extended" id="iceb1d6244a624999acc9e81afa057d6c_ConsolidatedStatementsofOperations">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_84a2fbd9-52ca-4168-94d1-5e9f7a86e772" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenuesAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_RevenuesAbstract_84a2fbd9-52ca-4168-94d1-5e9f7a86e772" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_9bf67cfc-ea5e-40ff-b3ce-d9f86658a6f9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_84a2fbd9-52ca-4168-94d1-5e9f7a86e772" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_9bf67cfc-ea5e-40ff-b3ce-d9f86658a6f9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingExpensesAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_e0a86068-63d0-4805-a18d-f061775e42ba" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_e0a86068-63d0-4805-a18d-f061775e42ba" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_320637ef-a8bd-45f1-ae03-5c7e3a1c2c3d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_320637ef-a8bd-45f1-ae03-5c7e3a1c2c3d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_ce58d23d-3035-4901-a8f3-11d7ca9fc03b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_ce58d23d-3035-4901-a8f3-11d7ca9fc03b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_bf75b174-dd7d-4f7b-b499-6991f65b850e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_bf75b174-dd7d-4f7b-b499-6991f65b850e" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_ad1c05f9-dd2e-4afd-9ce0-ee4a12b3d649" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_ad1c05f9-dd2e-4afd-9ce0-ee4a12b3d649" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetImpairmentCharges_d2488bfd-f1eb-4826-b154-e437e304a1fc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetImpairmentCharges"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_AssetImpairmentCharges_d2488bfd-f1eb-4826-b154-e437e304a1fc" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_23c6b707-c6e3-4280-9db3-7b0e312ae319" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingExpenses"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_a3169e5c-24a4-4326-ba34-95aef6b55da8" xlink:to="loc_us-gaap_OperatingExpenses_23c6b707-c6e3-4280-9db3-7b0e312ae319" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_887aa5e2-3fb5-43f9-a7b7-2c748b089b9f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingIncomeLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_OperatingIncomeLoss_887aa5e2-3fb5-43f9-a7b7-2c748b089b9f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpenseAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InterestIncomeNonoperating_70bf82cf-12ed-4142-9869-c946268c7a79" xlink:href="opk-20201231.xsd#opk_InterestIncomeNonoperating"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:to="loc_opk_InterestIncomeNonoperating_70bf82cf-12ed-4142-9869-c946268c7a79" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InterestExpenseNonoperating_b602c515-2f83-4441-8a0f-6e283b7498e9" xlink:href="opk-20201231.xsd#opk_InterestExpenseNonoperating"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:to="loc_opk_InterestExpenseNonoperating_b602c515-2f83-4441-8a0f-6e283b7498e9" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnDerivativeInstrumentsNetPretax_70b4b9ae-86bb-4ece-ae43-580c40ae7b44" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GainLossOnDerivativeInstrumentsNetPretax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:to="loc_us-gaap_GainLossOnDerivativeInstrumentsNetPretax_70b4b9ae-86bb-4ece-ae43-580c40ae7b44" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_aa8a68f2-41fd-4980-8902-44f276c4a1ec" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_aa8a68f2-41fd-4980-8902-44f276c4a1ec" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_6104787d-b622-491b-b2aa-be0793496eae" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NonoperatingIncomeExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_12890c4c-44f1-440f-aa8e-6391901d74ce" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_6104787d-b622-491b-b2aa-be0793496eae" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_c55b65fe-eae7-4429-babb-1f6382bdf6af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_c55b65fe-eae7-4429-babb-1f6382bdf6af" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_692e9dfb-edf9-4a0d-88c5-bf9cbbc55404" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_692e9dfb-edf9-4a0d-88c5-bf9cbbc55404" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_IncomeLossfromContinuingOperationsBeforeInvestmentsinInvesteesExtraordinaryItemsNetofTax_b511e1f5-f83d-49e8-b452-871b50b53969" xlink:href="opk-20201231.xsd#opk_IncomeLossfromContinuingOperationsBeforeInvestmentsinInvesteesExtraordinaryItemsNetofTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_opk_IncomeLossfromContinuingOperationsBeforeInvestmentsinInvesteesExtraordinaryItemsNetofTax_b511e1f5-f83d-49e8-b452-871b50b53969" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_IncomeLossfromEquityMethodInvestmentsNetofTax_77202e7f-9b6e-453e-bf29-8966df68a56b" xlink:href="opk-20201231.xsd#opk_IncomeLossfromEquityMethodInvestmentsNetofTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_opk_IncomeLossfromEquityMethodInvestmentsNetofTax_77202e7f-9b6e-453e-bf29-8966df68a56b" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_da9bbce9-e802-43ce-94cc-2c0205f67225" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_NetIncomeLoss_da9bbce9-e802-43ce-94cc-2c0205f67225" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasicAndDilutedAbstract_3276815a-2665-4fa8-8082-35bafaf80bc2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EarningsPerShareBasicAndDilutedAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_EarningsPerShareBasicAndDilutedAbstract_3276815a-2665-4fa8-8082-35bafaf80bc2" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasicAndDiluted_1ab87f80-d420-4370-96cb-cadac8d6d269" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EarningsPerShareBasicAndDiluted"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicAndDilutedAbstract_3276815a-2665-4fa8-8082-35bafaf80bc2" xlink:to="loc_us-gaap_EarningsPerShareBasicAndDiluted_1ab87f80-d420-4370-96cb-cadac8d6d269" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted_e5c1556a-c33f-4f76-8777-c8d5f4c4bdad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_WeightedAverageNumberOfShareOutstandingBasicAndDiluted_e5c1556a-c33f-4f76-8777-c8d5f4c4bdad" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_1b9e59c6-af66-4bc1-a9f3-2ac425fc2dc8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_8d1c14fd-dc3e-4819-9bd0-d8ea67fc251f" xlink:to="loc_us-gaap_StatementTable_1b9e59c6-af66-4bc1-a9f3-2ac425fc2dc8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_567ebd7a-47eb-493d-b1c4-525c81df94fe" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_1b9e59c6-af66-4bc1-a9f3-2ac425fc2dc8" xlink:to="loc_srt_ProductOrServiceAxis_567ebd7a-47eb-493d-b1c4-525c81df94fe" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_567ebd7a-47eb-493d-b1c4-525c81df94fe_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_567ebd7a-47eb-493d-b1c4-525c81df94fe" xlink:to="loc_srt_ProductsAndServicesDomain_567ebd7a-47eb-493d-b1c4-525c81df94fe_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_f2baa00f-ff86-4c51-aa0b-3cb97abcfbb5" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_567ebd7a-47eb-493d-b1c4-525c81df94fe" xlink:to="loc_srt_ProductsAndServicesDomain_f2baa00f-ff86-4c51-aa0b-3cb97abcfbb5" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_2e2e162a-e303-4e6d-97f7-e5d44c15ef63" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ServiceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2baa00f-ff86-4c51-aa0b-3cb97abcfbb5" xlink:to="loc_us-gaap_ServiceMember_2e2e162a-e303-4e6d-97f7-e5d44c15ef63" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_72204685-fdb8-4a48-94e5-d974b77a6f3a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2baa00f-ff86-4c51-aa0b-3cb97abcfbb5" xlink:to="loc_us-gaap_ProductMember_72204685-fdb8-4a48-94e5-d974b77a6f3a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TransferOfIntellectualPropertyAndOtherMember_307ebbb2-b200-4d29-8069-964d1f8550fe" xlink:href="opk-20201231.xsd#opk_TransferOfIntellectualPropertyAndOtherMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2baa00f-ff86-4c51-aa0b-3cb97abcfbb5" xlink:to="loc_opk_TransferOfIntellectualPropertyAndOtherMember_307ebbb2-b200-4d29-8069-964d1f8550fe" xlink:type="arc" order="2"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedStatementsofComprehensiveIncomeLoss" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedStatementsofComprehensiveIncomeLoss"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedStatementsofComprehensiveIncomeLoss" xlink:type="extended" id="i9e4df42d90b243d5a42f0fa2dfa55280_ConsolidatedStatementsofComprehensiveIncomeLoss"/>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedStatementsofEquity" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedStatementsofEquity"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedStatementsofEquity" xlink:type="extended" id="ib5e45252c2f7434ca1437a8499ef9177_ConsolidatedStatementsofEquity">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_ed5f19a4-f14c-4ff6-b63a-2525566a68b7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ed5f19a4-f14c-4ff6-b63a-2525566a68b7" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_22e262a2-f493-4da8-b0be-6cd220d63e50" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharesIssued"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_SharesIssued_22e262a2-f493-4da8-b0be-6cd220d63e50" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_920d7cf8-c1ca-4871-bf0a-3f4899c5a285" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockholdersEquity_920d7cf8-c1ca-4871-bf0a-3f4899c5a285" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_deeac9a4-21d2-4952-a052-a4e90143d9e9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_deeac9a4-21d2-4952-a052-a4e90143d9e9" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_467af20a-2614-4bf5-8d85-e88589c1e6ad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_467af20a-2614-4bf5-8d85-e88589c1e6ad" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_ed652f20-b5eb-43aa-b184-29e926ed95fa" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_ed652f20-b5eb-43aa-b184-29e926ed95fa" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities_bd8e5088-805b-4e16-9eba-ed9399bb5431" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities_bd8e5088-805b-4e16-9eba-ed9399bb5431" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt_7a825ee4-6243-42d9-baee-362cea906acf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt_7a825ee4-6243-42d9-baee-362cea906acf" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_c0d23f27-cc86-4803-9823-68e58dab5b67" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_c0d23f27-cc86-4803-9823-68e58dab5b67" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_416286f1-d209-4522-9e2e-1f198024792c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_416286f1-d209-4522-9e2e-1f198024792c" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_292bed26-dc2f-4163-9e9c-af2942e86f56" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_NetIncomeLoss_292bed26-dc2f-4163-9e9c-af2942e86f56" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_d20d97d1-b2b2-4d8a-b8a6-1649ae5f22b2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1dca72c2-fc12-49c6-923d-dda7b50a65b0" xlink:to="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_d20d97d1-b2b2-4d8a-b8a6-1649ae5f22b2" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_18c65a66-d3fc-4a59-ae13-8f2ce3ae3203" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharesIssued"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_12beda81-9f7b-4462-8cce-bfeaf6cab30a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountingStandardsUpdateExtensibleList_b3406131-5135-4c1f-82fd-e8dbf637e6c9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountingStandardsUpdateExtensibleList"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_ed5f19a4-f14c-4ff6-b63a-2525566a68b7" xlink:to="loc_us-gaap_AccountingStandardsUpdateExtensibleList_b3406131-5135-4c1f-82fd-e8dbf637e6c9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_3d43c4e9-bcd4-4e57-8780-c03406656bb2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_ed5f19a4-f14c-4ff6-b63a-2525566a68b7" xlink:to="loc_us-gaap_StatementTable_3d43c4e9-bcd4-4e57-8780-c03406656bb2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_44f21c44-1745-415d-9d0c-c3bfece39634" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_3d43c4e9-bcd4-4e57-8780-c03406656bb2" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_44f21c44-1745-415d-9d0c-c3bfece39634" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_44f21c44-1745-415d-9d0c-c3bfece39634_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_44f21c44-1745-415d-9d0c-c3bfece39634" xlink:to="loc_us-gaap_EquityComponentDomain_44f21c44-1745-415d-9d0c-c3bfece39634_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_44f21c44-1745-415d-9d0c-c3bfece39634" xlink:to="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_646ff55a-162a-43e3-acfa-899c6c658017" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:to="loc_us-gaap_CommonStockMember_646ff55a-162a-43e3-acfa-899c6c658017" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockMember_4e0750d0-8390-4ca0-8718-79ac0a4761a2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TreasuryStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:to="loc_us-gaap_TreasuryStockMember_4e0750d0-8390-4ca0-8718-79ac0a4761a2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_18ffcb6e-4d66-4510-8a1e-218282728d6b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_18ffcb6e-4d66-4510-8a1e-218282728d6b" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_d3bd65cf-470b-4695-bc04-d44075ac33af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_d3bd65cf-470b-4695-bc04-d44075ac33af" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_8f60eb73-62da-4305-8017-c13732e3fcc5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_46d4ae46-2dca-4e43-9c4a-d7273743d3f7" xlink:to="loc_us-gaap_RetainedEarningsMember_8f60eb73-62da-4305-8017-c13732e3fcc5" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_dc013c22-bbb5-4224-88fe-eb9bd2ccca21" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CumulativeEffectPeriodOfAdoptionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_3d43c4e9-bcd4-4e57-8780-c03406656bb2" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_dc013c22-bbb5-4224-88fe-eb9bd2ccca21" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_dc013c22-bbb5-4224-88fe-eb9bd2ccca21_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_dc013c22-bbb5-4224-88fe-eb9bd2ccca21" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_dc013c22-bbb5-4224-88fe-eb9bd2ccca21_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_8715f90b-dc1c-49f2-b8ac-d621367a9e92" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_dc013c22-bbb5-4224-88fe-eb9bd2ccca21" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_8715f90b-dc1c-49f2-b8ac-d621367a9e92" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_700d2e60-9fbe-4022-9654-95d478b706c3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_8715f90b-dc1c-49f2-b8ac-d621367a9e92" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_700d2e60-9fbe-4022-9654-95d478b706c3" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/ConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="opk-20201231.xsd#ConsolidatedStatementsofCashFlows"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ConsolidatedStatementsofCashFlows" xlink:type="extended" id="ic769e9de2c514957bd65f9ccc7a6d17c_ConsolidatedStatementsofCashFlows"/>
<link:roleRef roleURI="http://www.opko.com/role/BusinessandOrganization" xlink:type="simple" xlink:href="opk-20201231.xsd#BusinessandOrganization"/>
<link:definitionLink xlink:role="http://www.opko.com/role/BusinessandOrganization" xlink:type="extended" id="idda057a708bb4af589dd181118000fc5_BusinessandOrganization"/>
<link:roleRef roleURI="http://www.opko.com/role/BusinessandOrganizationNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#BusinessandOrganizationNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/BusinessandOrganizationNarrativeDetails" xlink:type="extended" id="i95d5ed84fb1a454eb182925aaa2b1c0f_BusinessandOrganizationNarrativeDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/ImpactofCOVID19" xlink:type="simple" xlink:href="opk-20201231.xsd#ImpactofCOVID19"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ImpactofCOVID19" xlink:type="extended" id="if962ed1e41dc41ceb01df39e6ba06722_ImpactofCOVID19"/>
<link:roleRef roleURI="http://www.opko.com/role/ImpactofCOVID19Details" xlink:type="simple" xlink:href="opk-20201231.xsd#ImpactofCOVID19Details"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ImpactofCOVID19Details" xlink:type="extended" id="i5b6462df57624dc98ba09094ae4c20b5_ImpactofCOVID19Details">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnusualOrInfrequentItemLineItems_df8e3bd3-4dc4-41f8-8cff-0101d873a125" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnusualOrInfrequentItemLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_IncreaseDecreaseInRevenueFromContractWithCustomerExcludingAssessedTax_1c8bdfbe-8518-4df6-a9e2-fa318da1c566" xlink:href="opk-20201231.xsd#opk_IncreaseDecreaseInRevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnusualOrInfrequentItemLineItems_df8e3bd3-4dc4-41f8-8cff-0101d873a125" xlink:to="loc_opk_IncreaseDecreaseInRevenueFromContractWithCustomerExcludingAssessedTax_1c8bdfbe-8518-4df6-a9e2-fa318da1c566" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChangeInTestingVolumePercent_9d550568-d683-460c-ad1c-374c7fc96929" xlink:href="opk-20201231.xsd#opk_ChangeInTestingVolumePercent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnusualOrInfrequentItemLineItems_df8e3bd3-4dc4-41f8-8cff-0101d873a125" xlink:to="loc_opk_ChangeInTestingVolumePercent_9d550568-d683-460c-ad1c-374c7fc96929" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfDebt_2c3456e4-31b9-4f70-b9c6-6a85a4d26750" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromIssuanceOfDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_UnusualOrInfrequentItemLineItems_df8e3bd3-4dc4-41f8-8cff-0101d873a125" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfDebt_2c3456e4-31b9-4f70-b9c6-6a85a4d26750" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnusualOrInfrequentItemTable_2938702c-cd4d-405f-aad0-b435e246b0cc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnusualOrInfrequentItemTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_UnusualOrInfrequentItemLineItems_df8e3bd3-4dc4-41f8-8cff-0101d873a125" xlink:to="loc_us-gaap_UnusualOrInfrequentItemTable_2938702c-cd4d-405f-aad0-b435e246b0cc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_7a24418f-5340-4b84-8523-0799466fa309" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_UnusualOrInfrequentItemTable_2938702c-cd4d-405f-aad0-b435e246b0cc" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_7a24418f-5340-4b84-8523-0799466fa309" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_7a24418f-5340-4b84-8523-0799466fa309_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_7a24418f-5340-4b84-8523-0799466fa309" xlink:to="loc_us-gaap_SegmentDomain_7a24418f-5340-4b84-8523-0799466fa309_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_fabb434a-112f-4bbe-a42a-9712d718198c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_7a24418f-5340-4b84-8523-0799466fa309" xlink:to="loc_us-gaap_SegmentDomain_fabb434a-112f-4bbe-a42a-9712d718198c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DiagnosticsMember_dc8897df-7f0a-477b-8419-57af001439d5" xlink:href="opk-20201231.xsd#opk_DiagnosticsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_fabb434a-112f-4bbe-a42a-9712d718198c" xlink:to="loc_opk_DiagnosticsMember_dc8897df-7f0a-477b-8419-57af001439d5" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_UnusualOrInfrequentItemTable_2938702c-cd4d-405f-aad0-b435e246b0cc" xlink:to="loc_us-gaap_DebtInstrumentAxis_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_f003a941-b6d2-420d-a4b1-fa572ac2c7b8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_f1379156-cbad-4cf4-a94a-1ecd9ef87a7d" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_f003a941-b6d2-420d-a4b1-fa572ac2c7b8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CMSAcceleratedAndAdvancedPaymentProgramCOVID19Member_f1e13bc6-ab49-4fd8-84f7-3754836a01cf" xlink:href="opk-20201231.xsd#opk_CMSAcceleratedAndAdvancedPaymentProgramCOVID19Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f003a941-b6d2-420d-a4b1-fa572ac2c7b8" xlink:to="loc_opk_CMSAcceleratedAndAdvancedPaymentProgramCOVID19Member_f1e13bc6-ab49-4fd8-84f7-3754836a01cf" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DistributionToHealthcareProvidersCOVID19Member_4bcffedc-a632-4188-9e37-74611a4f8a18" xlink:href="opk-20201231.xsd#opk_DistributionToHealthcareProvidersCOVID19Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f003a941-b6d2-420d-a4b1-fa572ac2c7b8" xlink:to="loc_opk_DistributionToHealthcareProvidersCOVID19Member_4bcffedc-a632-4188-9e37-74611a4f8a18" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_5dace848-30ee-484d-b387-d6a57020a30e" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_UnusualOrInfrequentItemTable_2938702c-cd4d-405f-aad0-b435e246b0cc" xlink:to="loc_srt_ProductOrServiceAxis_5dace848-30ee-484d-b387-d6a57020a30e" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_5dace848-30ee-484d-b387-d6a57020a30e_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_5dace848-30ee-484d-b387-d6a57020a30e" xlink:to="loc_srt_ProductsAndServicesDomain_5dace848-30ee-484d-b387-d6a57020a30e_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_56f0acc7-59cb-4024-b4b2-3024b1ea4fc2" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_5dace848-30ee-484d-b387-d6a57020a30e" xlink:to="loc_srt_ProductsAndServicesDomain_56f0acc7-59cb-4024-b4b2-3024b1ea4fc2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_fac62f3f-6111-4344-8b8c-b50d4777c855" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ServiceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_56f0acc7-59cb-4024-b4b2-3024b1ea4fc2" xlink:to="loc_us-gaap_ServiceMember_fac62f3f-6111-4344-8b8c-b50d4777c855" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/SummaryofSignificantAccountingPolicies" xlink:type="simple" xlink:href="opk-20201231.xsd#SummaryofSignificantAccountingPolicies"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SummaryofSignificantAccountingPolicies" xlink:type="extended" id="id815453d179349748afc9abb2bd0a7dc_SummaryofSignificantAccountingPolicies"/>
<link:roleRef roleURI="http://www.opko.com/role/SummaryofSignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="opk-20201231.xsd#SummaryofSignificantAccountingPoliciesPolicies"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SummaryofSignificantAccountingPoliciesPolicies" xlink:type="extended" id="i04f66b1405254ff3a6114992c4936f02_SummaryofSignificantAccountingPoliciesPolicies"/>
<link:roleRef roleURI="http://www.opko.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#SummaryofSignificantAccountingPoliciesNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="extended" id="i29f04b1ca45941b9b2de673f9f230a1b_SummaryofSignificantAccountingPoliciesNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:href="opk-20201231.xsd#opk_SummaryOfSignificantAccountingPoliciesLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWriteDown_f050a7b4-64f9-44c6-a631-4d43e5f1b380" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryWriteDown"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_InventoryWriteDown_f050a7b4-64f9-44c6-a631-4d43e5f1b380" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BusinessCombinationRecognizedIdentifiableAssetsAcquiredandLiabilitiesAssumedGoodwillandIntangibleAssets_43b87a7e-1370-4b57-b43b-4add30c56581" xlink:href="opk-20201231.xsd#opk_BusinessCombinationRecognizedIdentifiableAssetsAcquiredandLiabilitiesAssumedGoodwillandIntangibleAssets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_opk_BusinessCombinationRecognizedIdentifiableAssetsAcquiredandLiabilitiesAssumedGoodwillandIntangibleAssets_43b87a7e-1370-4b57-b43b-4add30c56581" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_684e22ee-0be5-4f0c-b851-28d2612cbf6f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Goodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_Goodwill_684e22ee-0be5-4f0c-b851-28d2612cbf6f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill_92daef74-183d-43a4-a29d-ea3dd9160560" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill_92daef74-183d-43a4-a29d-ea3dd9160560" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetImpairmentCharges_d8f12559-3f1e-471f-9a99-33641f4fa59c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetImpairmentCharges"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_AssetImpairmentCharges_d8f12559-3f1e-471f-9a99-33641f4fa59c" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_cd0355bc-bb5e-4827-a51c-35746382de98" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_cd0355bc-bb5e-4827-a51c-35746382de98" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_d9488ccc-7c68-4e7d-95be-de6a00acb4d3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillImpairmentLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_d9488ccc-7c68-4e7d-95be-de6a00acb4d3" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_66399780-e987-4135-8dd1-a6b5fcaa917c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_66399780-e987-4135-8dd1-a6b5fcaa917c" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_f3a37ef2-ccbc-4269-aa9f-f7637b1503b2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_f3a37ef2-ccbc-4269-aa9f-f7637b1503b2" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_7773df77-7546-4e76-8d6f-d0166d5d9656" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_7773df77-7546-4e76-8d6f-d0166d5d9656" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_53db3d64-b319-4b5a-a633-833465f75626" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_53db3d64-b319-4b5a-a633-833465f75626" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_428cff4a-be00-46e2-9105-d8516f98c8f2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_428cff4a-be00-46e2-9105-d8516f98c8f2" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_7490affc-d4aa-4a78-8598-414d4939262b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_7490affc-d4aa-4a78-8598-414d4939262b" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive_90c7443e-1325-485d-96ac-c2bb74a17260" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFive_90c7443e-1325-485d-96ac-c2bb74a17260" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_e23e66c3-9143-46fd-adde-c9954dbfffbd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_e23e66c3-9143-46fd-adde-c9954dbfffbd" xlink:type="arc" order="14"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_94eb336e-3c6e-4212-aa71-ea1c552d8adf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Depreciation"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_Depreciation_94eb336e-3c6e-4212-aa71-ea1c552d8adf" xlink:type="arc" order="15"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued_47bf234a-8989-4008-8462-5475354ed72e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestAccrued_47bf234a-8989-4008-8462-5475354ed72e" xlink:type="arc" order="16"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExaminationEstimateOfPossibleLoss_c6d58ee9-0736-417a-afa1-4009d9d80ecb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeTaxExaminationEstimateOfPossibleLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_IncomeTaxExaminationEstimateOfPossibleLoss_c6d58ee9-0736-417a-afa1-4009d9d80ecb" xlink:type="arc" order="17"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_e1bcdfbe-134d-46cb-b692-b85fee15ae78" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskPercentage1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_e1bcdfbe-134d-46cb-b692-b85fee15ae78" xlink:type="arc" order="18"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_9fc1d140-346e-4ee0-aac4-287b7ebb2cc4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_9fc1d140-346e-4ee0-aac4-287b7ebb2cc4" xlink:type="arc" order="19"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProvisionForDoubtfulAccounts_981de440-9ca8-4821-9e73-ebd587e5ae8d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProvisionForDoubtfulAccounts"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_ProvisionForDoubtfulAccounts_981de440-9ca8-4821-9e73-ebd587e5ae8d" xlink:type="arc" order="20"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_9f840d68-93ea-4daa-949e-bb4217986bb0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensation"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_ShareBasedCompensation_9f840d68-93ea-4daa-949e-bb4217986bb0" xlink:type="arc" order="21"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfReportableSegments_3bee9af9-386b-484f-b189-e633cc811e55" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NumberOfReportableSegments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_NumberOfReportableSegments_3bee9af9-386b-484f-b189-e633cc811e55" xlink:type="arc" order="22"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignCurrencyTransactionGainLossBeforeTax_b0f654fb-b646-429b-baef-ef572ef301b2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForeignCurrencyTransactionGainLossBeforeTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_us-gaap_ForeignCurrencyTransactionGainLossBeforeTax_b0f654fb-b646-429b-baef-ef572ef301b2" xlink:type="arc" order="23"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:href="opk-20201231.xsd#opk_SummaryOfSignificantAccountingPoliciesTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_3056df7d-953a-47ee-b3cb-f2eea7baa060" xlink:to="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_e4578f74-b1c6-456a-95da-a15bea49bbbd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_e4578f74-b1c6-456a-95da-a15bea49bbbd" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_e4578f74-b1c6-456a-95da-a15bea49bbbd_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_e4578f74-b1c6-456a-95da-a15bea49bbbd" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_e4578f74-b1c6-456a-95da-a15bea49bbbd_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bc73e9f9-5827-4912-84e9-87ba3eb91c39" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_e4578f74-b1c6-456a-95da-a15bea49bbbd" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bc73e9f9-5827-4912-84e9-87ba3eb91c39" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_d9013ee9-a3d4-4cc6-be53-4eb014c4a494" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bc73e9f9-5827-4912-84e9-87ba3eb91c39" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_d9013ee9-a3d4-4cc6-be53-4eb014c4a494" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_fe58ed19-c6c5-4af0-a090-2ad1dae3075f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_fe58ed19-c6c5-4af0-a090-2ad1dae3075f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_fe58ed19-c6c5-4af0-a090-2ad1dae3075f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_fe58ed19-c6c5-4af0-a090-2ad1dae3075f" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_fe58ed19-c6c5-4af0-a090-2ad1dae3075f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_07737b41-5f23-4552-83bd-c9ab14bbe672" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_fe58ed19-c6c5-4af0-a090-2ad1dae3075f" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_07737b41-5f23-4552-83bd-c9ab14bbe672" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_8010197c-bed2-46d5-bb18-59f401296b9a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_07737b41-5f23-4552-83bd-c9ab14bbe672" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_8010197c-bed2-46d5-bb18-59f401296b9a" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TrademarksMember_49a92bc9-704b-4158-aaca-090c55fa81a7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TrademarksMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_07737b41-5f23-4552-83bd-c9ab14bbe672" xlink:to="loc_us-gaap_TrademarksMember_49a92bc9-704b-4158-aaca-090c55fa81a7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_234a3130-2627-4210-b66a-ecfaf6ba471f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_234a3130-2627-4210-b66a-ecfaf6ba471f" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_234a3130-2627-4210-b66a-ecfaf6ba471f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_234a3130-2627-4210-b66a-ecfaf6ba471f" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_234a3130-2627-4210-b66a-ecfaf6ba471f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_4adc9e28-5e4b-4ca4-bd29-602ec256bec6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_234a3130-2627-4210-b66a-ecfaf6ba471f" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_4adc9e28-5e4b-4ca4-bd29-602ec256bec6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_24543a58-0801-4bce-97e7-2de7e3d538dd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsReceivableMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_4adc9e28-5e4b-4ca4-bd29-602ec256bec6" xlink:to="loc_us-gaap_AccountsReceivableMember_24543a58-0801-4bce-97e7-2de7e3d538dd" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_df695078-bb0f-45b0-8fa0-6bb176b23936" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_df695078-bb0f-45b0-8fa0-6bb176b23936" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_df695078-bb0f-45b0-8fa0-6bb176b23936_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_df695078-bb0f-45b0-8fa0-6bb176b23936" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_df695078-bb0f-45b0-8fa0-6bb176b23936_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_df89b69d-b5f9-4705-9206-9ac755207749" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_df695078-bb0f-45b0-8fa0-6bb176b23936" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_df89b69d-b5f9-4705-9206-9ac755207749" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GovernmentContractsConcentrationRiskMember_4ab38a92-7621-4cb2-900a-cef6fda24520" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GovernmentContractsConcentrationRiskMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_df89b69d-b5f9-4705-9206-9ac755207749" xlink:to="loc_us-gaap_GovernmentContractsConcentrationRiskMember_4ab38a92-7621-4cb2-900a-cef6fda24520" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicConcentrationRiskMember_d4da2e39-36b2-4b0d-98ec-35c92f3f93a8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GeographicConcentrationRiskMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_df89b69d-b5f9-4705-9206-9ac755207749" xlink:to="loc_us-gaap_GeographicConcentrationRiskMember_d4da2e39-36b2-4b0d-98ec-35c92f3f93a8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_6f1b3ac5-069d-41fe-a414-72c2df4fb9aa" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CustomerConcentrationRiskMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_df89b69d-b5f9-4705-9206-9ac755207749" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_6f1b3ac5-069d-41fe-a414-72c2df4fb9aa" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_735a8d70-251b-4bb2-8b04-071c80543d37" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_735a8d70-251b-4bb2-8b04-071c80543d37" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_735a8d70-251b-4bb2-8b04-071c80543d37_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_735a8d70-251b-4bb2-8b04-071c80543d37" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_735a8d70-251b-4bb2-8b04-071c80543d37_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_735a8d70-251b-4bb2-8b04-071c80543d37" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerSoftwareIntangibleAssetMember_2fcaf145-c4ab-49da-a06a-e7de2eb4d204" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComputerSoftwareIntangibleAssetMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:to="loc_us-gaap_ComputerSoftwareIntangibleAssetMember_2fcaf145-c4ab-49da-a06a-e7de2eb4d204" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_MachineryAndEquipmentMember_384f76eb-e44c-4852-b674-c3a5f5ffaeda" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MachineryAndEquipmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:to="loc_us-gaap_MachineryAndEquipmentMember_384f76eb-e44c-4852-b674-c3a5f5ffaeda" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_ce9083b0-861b-477f-a98d-91e0574e3758" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FurnitureAndFixturesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_ce9083b0-861b-477f-a98d-91e0574e3758" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandBuildingsAndImprovementsMember_39d47e6d-4135-4773-8793-f5de2b359db2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LandBuildingsAndImprovementsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:to="loc_us-gaap_LandBuildingsAndImprovementsMember_39d47e6d-4135-4773-8793-f5de2b359db2" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransportationEquipmentMember_a59be328-e317-4397-9a2e-f7546178f264" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TransportationEquipmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4cbd9cb1-770b-4d80-9167-a9495d600341" xlink:to="loc_us-gaap_TransportationEquipmentMember_a59be328-e317-4397-9a2e-f7546178f264" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_12ca4dca-7495-4450-9d8c-d332ccbdf505" xlink:to="loc_srt_RangeAxis_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207" xlink:to="loc_srt_RangeMember_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_cb293c79-cdd5-4e4c-b15c-3f0912c2da49" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_fdcbb7e1-f889-4dee-95bd-8dc1b98a8207" xlink:to="loc_srt_RangeMember_cb293c79-cdd5-4e4c-b15c-3f0912c2da49" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_a7f9a8c3-7bcc-422a-a240-d8a324940a96" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_cb293c79-cdd5-4e4c-b15c-3f0912c2da49" xlink:to="loc_srt_MinimumMember_a7f9a8c3-7bcc-422a-a240-d8a324940a96" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_0210146a-b879-4463-9562-93171dfc0165" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_cb293c79-cdd5-4e4c-b15c-3f0912c2da49" xlink:to="loc_srt_MaximumMember_0210146a-b879-4463-9562-93171dfc0165" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/IncomelossPerShare" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomelossPerShare"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomelossPerShare" xlink:type="extended" id="if1ed94c7728440b1ac5070067eb99fed_IncomelossPerShare"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomelossPerShareNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomelossPerShareNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomelossPerShareNarrativeDetails" xlink:type="extended" id="i49cbb697cb3c476db6c05d8ec44fc606_IncomelossPerShareNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_611d1d23-9adf-4a4e-87a0-ef97529a8c60" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_611d1d23-9adf-4a4e-87a0-ef97529a8c60" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_9d2be359-b4c8-43a2-8be2-9678b716a82d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_9d2be359-b4c8-43a2-8be2-9678b716a82d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercised_62f3899f-de4f-4850-9cf7-48f81e42b014" xlink:href="opk-20201231.xsd#opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercised"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercised_62f3899f-de4f-4850-9cf7-48f81e42b014" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercisedNetofSharesSurrenderedinLieuofCashPayment_8a60e37d-febd-4db0-9e6b-f32c443e35dc" xlink:href="opk-20201231.xsd#opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercisedNetofSharesSurrenderedinLieuofCashPayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_opk_StockIssuedDuringPeriodSharesStockOptionsandWarrantsExercisedNetofSharesSurrenderedinLieuofCashPayment_8a60e37d-febd-4db0-9e6b-f32c443e35dc" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SharesSurrenderedInLieuOfCashPayment_ef6909b5-05c3-4b8a-8c85-1d40912c5e40" xlink:href="opk-20201231.xsd#opk_SharesSurrenderedInLieuOfCashPayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_opk_SharesSurrenderedInLieuOfCashPayment_ef6909b5-05c3-4b8a-8c85-1d40912c5e40" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0b9bb9f-9f73-444b-b0e9-6efe8d704d8a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_e104a5c2-db55-42bd-a29a-3082483a2e4f" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0b9bb9f-9f73-444b-b0e9-6efe8d704d8a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_58141e13-28f0-42c7-bd4e-7f0b122ffb48" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0b9bb9f-9f73-444b-b0e9-6efe8d704d8a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_58141e13-28f0-42c7-bd4e-7f0b122ffb48" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_58141e13-28f0-42c7-bd4e-7f0b122ffb48_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_58141e13-28f0-42c7-bd4e-7f0b122ffb48" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_58141e13-28f0-42c7-bd4e-7f0b122ffb48_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_ffd9513a-d0a5-4971-8c27-9517cd4b3028" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_58141e13-28f0-42c7-bd4e-7f0b122ffb48" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_ffd9513a-d0a5-4971-8c27-9517cd4b3028" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_3833d07c-ac20-4525-a6f5-ea9857dce674" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_ffd9513a-d0a5-4971-8c27-9517cd4b3028" xlink:to="loc_us-gaap_CommonStockMember_3833d07c-ac20-4525-a6f5-ea9857dce674" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/Investments" xlink:type="simple" xlink:href="opk-20201231.xsd#Investments"/>
<link:definitionLink xlink:role="http://www.opko.com/role/Investments" xlink:type="extended" id="i57899818dc1941c9b22c21d9ef5cbe4b_Investments"/>
<link:roleRef roleURI="http://www.opko.com/role/InvestmentsTables" xlink:type="simple" xlink:href="opk-20201231.xsd#InvestmentsTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/InvestmentsTables" xlink:type="extended" id="idbdde94a6c5f4bf688d3c758853c2e33_InvestmentsTables"/>
<link:roleRef roleURI="http://www.opko.com/role/InvestmentsAccountingMethodCarryingValueandUnderlyingEquityinNetAssetsofUnconsolidatedInvestmentsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#InvestmentsAccountingMethodCarryingValueandUnderlyingEquityinNetAssetsofUnconsolidatedInvestmentsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/InvestmentsAccountingMethodCarryingValueandUnderlyingEquityinNetAssetsofUnconsolidatedInvestmentsDetails" xlink:type="extended" id="i98a31bc20d254bfbb7efb5d8fc835a14_InvestmentsAccountingMethodCarryingValueandUnderlyingEquityinNetAssetsofUnconsolidatedInvestmentsDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/InvestmentsNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#InvestmentsNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/InvestmentsNarrativeDetails" xlink:type="extended" id="i996935afb0024be49bb4e9b1bbbfae38_InvestmentsNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_423bc70e-28ed-4330-9b3c-2d93b3ea28ff" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_423bc70e-28ed-4330-9b3c-2d93b3ea28ff" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_4d4b6b6d-5312-427a-af76-3e364dfc5dbc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Assets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_Assets_4d4b6b6d-5312-427a-af76-3e364dfc5dbc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_e9bc6b03-3240-450c-8e20-d4b62f1d13d7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Liabilities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_Liabilities_e9bc6b03-3240-450c-8e20-d4b62f1d13d7" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_ce74c6d4-5d73-401f-9330-c8e3ca9c9a29" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProfitLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_ProfitLoss_ce74c6d4-5d73-401f-9330-c8e3ca9c9a29" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment_aed769a0-ba1a-4927-b47a-d9322ccf4c1e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment_aed769a0-ba1a-4927-b47a-d9322ccf4c1e" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentQuotedMarketValue_de87bdc5-b369-4fd9-a5c3-ff007fc8fd1a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentQuotedMarketValue"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_EquityMethodInvestmentQuotedMarketValue_de87bdc5-b369-4fd9-a5c3-ff007fc8fd1a" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EquitySecurityFVNIOwnershipPercent_e80718d5-9073-40fe-9f21-53db3c794f10" xlink:href="opk-20201231.xsd#opk_EquitySecurityFVNIOwnershipPercent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_opk_EquitySecurityFVNIOwnershipPercent_e80718d5-9073-40fe-9f21-53db3c794f10" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_f965009b-8396-4cc6-82e1-b64d8f3593ad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_f965009b-8396-4cc6-82e1-b64d8f3593ad" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireEquityMethodInvestments_91750eb8-a85e-43a3-a76e-f963683600fc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireEquityMethodInvestments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_PaymentsToAcquireEquityMethodInvestments_91750eb8-a85e-43a3-a76e-f963683600fc" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentOwnedBalanceShares_d2564541-389e-4861-b74d-598f81a9c051" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentOwnedBalanceShares"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_InvestmentOwnedBalanceShares_d2564541-389e-4861-b74d-598f81a9c051" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_2adcdd1d-f942-4799-aef2-a32dbbdf2be2" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_668fe00f-9d49-4a34-8c02-a18bf0a49f0d" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_668fe00f-9d49-4a34-8c02-a18bf0a49f0d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_668fe00f-9d49-4a34-8c02-a18bf0a49f0d_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_668fe00f-9d49-4a34-8c02-a18bf0a49f0d" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_668fe00f-9d49-4a34-8c02-a18bf0a49f0d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_668fe00f-9d49-4a34-8c02-a18bf0a49f0d" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PharmsynthezMember_1d4a3b88-235b-4c62-869f-f144cf505f9f" xlink:href="opk-20201231.xsd#opk_PharmsynthezMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_PharmsynthezMember_1d4a3b88-235b-4c62-869f-f144cf505f9f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CocrystalPharmaInc.Member_3c372f87-49d5-4a70-a2d2-0ae04b88ef87" xlink:href="opk-20201231.xsd#opk_CocrystalPharmaInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_CocrystalPharmaInc.Member_3c372f87-49d5-4a70-a2d2-0ae04b88ef87" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NIMSMember_b912a647-5ec8-4cf5-ba2c-5d00ddee0ab6" xlink:href="opk-20201231.xsd#opk_NIMSMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_NIMSMember_b912a647-5ec8-4cf5-ba2c-5d00ddee0ab6" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NeovascMember_022a43bd-d63e-4b26-a14d-2f240b774ac6" xlink:href="opk-20201231.xsd#opk_NeovascMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_NeovascMember_022a43bd-d63e-4b26-a14d-2f240b774ac6" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InCellDxIncMember_826a716d-868a-42d6-9420-3d64dc1cf9e8" xlink:href="opk-20201231.xsd#opk_InCellDxIncMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_InCellDxIncMember_826a716d-868a-42d6-9420-3d64dc1cf9e8" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioCardiaInc.Member_db873ac1-9e9a-4df4-a296-3c0765dcaa03" xlink:href="opk-20201231.xsd#opk_BioCardiaInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_BioCardiaInc.Member_db873ac1-9e9a-4df4-a296-3c0765dcaa03" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_XeneticBiosciencesInc.Member_f6a56167-4f69-4257-9ab7-423fe914f0bb" xlink:href="opk-20201231.xsd#opk_XeneticBiosciencesInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_XeneticBiosciencesInc.Member_f6a56167-4f69-4257-9ab7-423fe914f0bb" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PhioPharmaceuticalsMember_25133575-3688-496f-8539-370a98297fee" xlink:href="opk-20201231.xsd#opk_PhioPharmaceuticalsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_PhioPharmaceuticalsMember_25133575-3688-496f-8539-370a98297fee" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_VBIVaccinesIncMember_b2508510-7673-4fa2-8290-d11a31783d7d" xlink:href="opk-20201231.xsd#opk_VBIVaccinesIncMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_VBIVaccinesIncMember_b2508510-7673-4fa2-8290-d11a31783d7d" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChromadexCorporationMember_2bd82396-9457-4a9a-806b-5032a74b32e5" xlink:href="opk-20201231.xsd#opk_ChromadexCorporationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_ChromadexCorporationMember_2bd82396-9457-4a9a-806b-5032a74b32e5" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MabVaxTherapeuticsHoldingsInc.Member_dadf7afc-c07f-45f5-a263-885e2015a122" xlink:href="opk-20201231.xsd#opk_MabVaxTherapeuticsHoldingsInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_MabVaxTherapeuticsHoldingsInc.Member_dadf7afc-c07f-45f5-a263-885e2015a122" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EloxxPharmaceuticalsMember_3dd6f782-b881-424c-bd6f-a862177fd109" xlink:href="opk-20201231.xsd#opk_EloxxPharmaceuticalsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_EloxxPharmaceuticalsMember_3dd6f782-b881-424c-bd6f-a862177fd109" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CocrystalMember_0ef2d7f0-4a48-49ad-b8b8-d1752780cf4e" xlink:href="opk-20201231.xsd#opk_CocrystalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_CocrystalMember_0ef2d7f0-4a48-49ad-b8b8-d1752780cf4e" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InCellDxInc.Member_ae2e1dd2-af64-4a0f-bd75-1a4d2196cbd9" xlink:href="opk-20201231.xsd#opk_InCellDxInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_InCellDxInc.Member_ae2e1dd2-af64-4a0f-bd75-1a4d2196cbd9" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ZebraMember_2df58808-c456-4128-a417-8fce3dfc2468" xlink:href="opk-20201231.xsd#opk_ZebraMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_ZebraMember_2df58808-c456-4128-a417-8fce3dfc2468" xlink:type="arc" order="14"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DetectGenomixMember_f3733184-986d-42e5-b4cf-9ecc1257e48b" xlink:href="opk-20201231.xsd#opk_DetectGenomixMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_db4a730e-f6b8-42c2-8b5d-30b331ba7d9c" xlink:to="loc_opk_DetectGenomixMember_f3733184-986d-42e5-b4cf-9ecc1257e48b" xlink:type="arc" order="15"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9d5d72ea-5dc7-4a79-aca1-00ee110368c5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_1697b4cf-2bbe-49f1-a9fb-b5ca2e753e7d" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9d5d72ea-5dc7-4a79-aca1-00ee110368c5" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EloxxPharmaceuticalsMember_46ed1c91-4acb-42da-b436-de5c9c3b7e90" xlink:href="opk-20201231.xsd#opk_EloxxPharmaceuticalsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9d5d72ea-5dc7-4a79-aca1-00ee110368c5" xlink:to="loc_opk_EloxxPharmaceuticalsMember_46ed1c91-4acb-42da-b436-de5c9c3b7e90" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_60af2eb7-90f9-4f14-aacd-249799bcdba1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:to="loc_us-gaap_StatementClassOfStockAxis_60af2eb7-90f9-4f14-aacd-249799bcdba1" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_60af2eb7-90f9-4f14-aacd-249799bcdba1_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_60af2eb7-90f9-4f14-aacd-249799bcdba1" xlink:to="loc_us-gaap_ClassOfStockDomain_60af2eb7-90f9-4f14-aacd-249799bcdba1_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_f53aded6-c413-4dcc-872d-51935f4089d3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_60af2eb7-90f9-4f14-aacd-249799bcdba1" xlink:to="loc_us-gaap_ClassOfStockDomain_f53aded6-c413-4dcc-872d-51935f4089d3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_5bbc9964-ec4d-4d7f-a242-6bf896962085" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeriesAPreferredStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_f53aded6-c413-4dcc-872d-51935f4089d3" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_5bbc9964-ec4d-4d7f-a242-6bf896962085" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockMember_a9d7eeb2-77f6-4bf4-8d0e-daf3eaec7625" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestrictedStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_f53aded6-c413-4dcc-872d-51935f4089d3" xlink:to="loc_us-gaap_RestrictedStockMember_a9d7eeb2-77f6-4bf4-8d0e-daf3eaec7625" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeAxis_b6c5c13d-345d-4b03-8729-e761f89fb887" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:to="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeAxis_b6c5c13d-345d-4b03-8729-e761f89fb887" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain_b6c5c13d-345d-4b03-8729-e761f89fb887_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeAxis_b6c5c13d-345d-4b03-8729-e761f89fb887" xlink:to="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain_b6c5c13d-345d-4b03-8729-e761f89fb887_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain_9c209c1a-4f3b-4b2d-b67a-0da1ddecb20e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeAxis_b6c5c13d-345d-4b03-8729-e761f89fb887" xlink:to="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain_9c209c1a-4f3b-4b2d-b67a-0da1ddecb20e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeOrGroupOfInvesteesMember_55153f23-fa6a-4e76-afbe-8efda10527d3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeOrGroupOfInvesteesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeDomain_9c209c1a-4f3b-4b2d-b67a-0da1ddecb20e" xlink:to="loc_us-gaap_EquityMethodInvestmentNonconsolidatedInvesteeOrGroupOfInvesteesMember_55153f23-fa6a-4e76-afbe-8efda10527d3" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesAxis_598d5cdb-5202-4414-96dc-ffd837253e5b" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_548fa1b8-1e8f-418f-b34e-1b8ad3240011" xlink:to="loc_srt_ConsolidatedEntitiesAxis_598d5cdb-5202-4414-96dc-ffd837253e5b" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_598d5cdb-5202-4414-96dc-ffd837253e5b_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidatedEntitiesAxis_598d5cdb-5202-4414-96dc-ffd837253e5b" xlink:to="loc_srt_ConsolidatedEntitiesDomain_598d5cdb-5202-4414-96dc-ffd837253e5b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_211fce8d-9762-4eb5-9ec3-4c51c9ff8dc6" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidatedEntitiesAxis_598d5cdb-5202-4414-96dc-ffd837253e5b" xlink:to="loc_srt_ConsolidatedEntitiesDomain_211fce8d-9762-4eb5-9ec3-4c51c9ff8dc6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_51bbc76e-8ed0-4f03-893e-fe44960280a7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidatedEntitiesDomain_211fce8d-9762-4eb5-9ec3-4c51c9ff8dc6" xlink:to="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_51bbc76e-8ed0-4f03-893e-fe44960280a7" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/InvestmentsScheduleofNetGainsandLossesonEquitySecuritiesDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#InvestmentsScheduleofNetGainsandLossesonEquitySecuritiesDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/InvestmentsScheduleofNetGainsandLossesonEquitySecuritiesDetails" xlink:type="extended" id="i1f904c0d94cd4ef5ae5aae0517ace306_InvestmentsScheduleofNetGainsandLossesonEquitySecuritiesDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptions" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptions"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptions" xlink:type="extended" id="ib89c39f93ed34ac0aace225a40d0a2e2_CompositionofCertainFinancialStatementCaptions"/>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsTables" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptionsTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsTables" xlink:type="extended" id="i8ee0af631f53400592488c6dba7fc444_CompositionofCertainFinancialStatementCaptionsTables"/>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsCompositionofCertainFinancialStatementCaptionsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptionsCompositionofCertainFinancialStatementCaptionsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsCompositionofCertainFinancialStatementCaptionsDetails" xlink:type="extended" id="i6fe3e66bff5d4f838288009498e22f65_CompositionofCertainFinancialStatementCaptionsCompositionofCertainFinancialStatementCaptionsDetails">
<link:loc xlink:type="locator" xlink:label="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CondensedFinancialStatementsCaptionsLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetAbstract_4d3a92f5-43ca-4c8e-bf3f-05d405b7a496" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsReceivableNetAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_AccountsReceivableNetAbstract_4d3a92f5-43ca-4c8e-bf3f-05d405b7a496" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableGrossCurrent_f38a4cc5-af70-4c01-bfe9-b10aebf95ac0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsReceivableGrossCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsReceivableNetAbstract_4d3a92f5-43ca-4c8e-bf3f-05d405b7a496" xlink:to="loc_us-gaap_AccountsReceivableGrossCurrent_f38a4cc5-af70-4c01-bfe9-b10aebf95ac0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_0cdf2225-45f9-4c9b-aff0-4e1ae7d43caf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsReceivableNetAbstract_4d3a92f5-43ca-4c8e-bf3f-05d405b7a496" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_0cdf2225-45f9-4c9b-aff0-4e1ae7d43caf" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_19f6279b-1726-447e-acac-7f61bbeeff68" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsReceivableNetCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsReceivableNetAbstract_4d3a92f5-43ca-4c8e-bf3f-05d405b7a496" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_19f6279b-1726-447e-acac-7f61bbeeff68" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryNetAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherInventorySupplies_b450c225-3ee7-4355-a9dd-835b4957c33f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherInventorySupplies"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_OtherInventorySupplies_b450c225-3ee7-4355-a9dd-835b4957c33f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryFinishedGoods_2f151da4-0f45-4bc7-ab27-efa34cc7210a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryFinishedGoods"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_InventoryFinishedGoods_2f151da4-0f45-4bc7-ab27-efa34cc7210a" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWorkInProcess_34df3e94-ef1b-4453-8e90-c5b1a8a5ad99" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryWorkInProcess"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_InventoryWorkInProcess_34df3e94-ef1b-4453-8e90-c5b1a8a5ad99" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryRawMaterials_813153a3-ccf5-4552-9383-554b387d261a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryRawMaterials"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_InventoryRawMaterials_813153a3-ccf5-4552-9383-554b387d261a" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryValuationReserves_e58ce7f6-0281-49c6-994c-21c2c01df38d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryValuationReserves"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_InventoryValuationReserves_e58ce7f6-0281-49c6-994c-21c2c01df38d" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_8a49d6dc-9d7e-4827-94f4-adc9d4f9fad1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryNet"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InventoryNetAbstract_6b4e3fb8-c55b-4f0e-ad65-a2fca06fecd8" xlink:to="loc_us-gaap_InventoryNet_8a49d6dc-9d7e-4827-94f4-adc9d4f9fad1" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TaxesRecoverableCurrent_34b50845-2215-463c-904e-d020179f6dfc" xlink:href="opk-20201231.xsd#opk_TaxesRecoverableCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_opk_TaxesRecoverableCurrent_34b50845-2215-463c-904e-d020179f6dfc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsAndOtherReceivablesNetCurrent_401bb35e-0b65-4281-ab75-8c3dea767802" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsAndOtherReceivablesNetCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_us-gaap_AccountsAndOtherReceivablesNetCurrent_401bb35e-0b65-4281-ab75-8c3dea767802" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Supplies_f3785df2-92b2-43ce-b2b5-8d68a2230593" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Supplies"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_us-gaap_Supplies_f3785df2-92b2-43ce-b2b5-8d68a2230593" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidInsurance_f132c1bc-04bb-4850-b8e0-7e25b2a189b8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidInsurance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_us-gaap_PrepaidInsurance_f132c1bc-04bb-4850-b8e0-7e25b2a189b8" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsCurrent_ff7b02e0-85ae-4b9c-932e-a2828f68d9da" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_us-gaap_OtherAssetsCurrent_ff7b02e0-85ae-4b9c-932e-a2828f68d9da" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_03cd43bf-e522-4e81-901f-2cf0a724f22e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrentAbstract_44749f21-def2-4848-a0b6-121ebd7185d8" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_03cd43bf-e522-4e81-901f-2cf0a724f22e" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNetAbstract_e56cbde8-b7b5-485a-b26c-11918bbc4b53" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNetAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNetAbstract_e56cbde8-b7b5-485a-b26c-11918bbc4b53" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_fe7f5e55-f169-45c3-aece-9cea5d3e5d0c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNetAbstract_e56cbde8-b7b5-485a-b26c-11918bbc4b53" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_fe7f5e55-f169-45c3-aece-9cea5d3e5d0c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_e60ff0b9-9841-4d69-81b2-24cbe85886f8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNetAbstract_e56cbde8-b7b5-485a-b26c-11918bbc4b53" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_e60ff0b9-9841-4d69-81b2-24cbe85886f8" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_53a75c86-511e-4675-9fd7-9df97a271657" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentNetAbstract_e56cbde8-b7b5-485a-b26c-11918bbc4b53" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_53a75c86-511e-4675-9fd7-9df97a271657" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNetAbstract_2e966b9b-5da6-4136-b7a1-19cc0c370c70" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNetAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNetAbstract_2e966b9b-5da6-4136-b7a1-19cc0c370c70" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_3e8022c6-1e73-4477-85cf-b3d29f9f1857" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsNetAbstract_2e966b9b-5da6-4136-b7a1-19cc0c370c70" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_3e8022c6-1e73-4477-85cf-b3d29f9f1857" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_21e561c7-2e88-46dc-856e-120177e14036" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsNetAbstract_2e966b9b-5da6-4136-b7a1-19cc0c370c70" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_21e561c7-2e88-46dc-856e-120177e14036" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_b397ca7c-7cb7-4a58-bf18-7e63449f825e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsNetAbstract_2e966b9b-5da6-4136-b7a1-19cc0c370c70" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_b397ca7c-7cb7-4a58-bf18-7e63449f825e" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrentAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InventoryReceivedNotInvoicedCurrent_fb4d846c-dfae-449c-8df5-645787d13b32" xlink:href="opk-20201231.xsd#opk_InventoryReceivedNotInvoicedCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_opk_InventoryReceivedNotInvoicedCurrent_fb4d846c-dfae-449c-8df5-645787d13b32" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedEmployeeBenefitsCurrent_f7ffa2ad-e7e9-41a5-84f9-46fcf24279cd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedEmployeeBenefitsCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_AccruedEmployeeBenefitsCurrent_f7ffa2ad-e7e9-41a5-84f9-46fcf24279cd" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_6433aef7-80d5-4328-959b-e80772e88195" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_6433aef7-80d5-4328-959b-e80772e88195" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AccruedCommitmentsandContingenciesCurrent_c74c25c4-4370-4614-979f-5f708dc27654" xlink:href="opk-20201231.xsd#opk_AccruedCommitmentsandContingenciesCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_opk_AccruedCommitmentsandContingenciesCurrent_c74c25c4-4370-4614-979f-5f708dc27654" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AccruedClinicalTrialsCurrent_5a5c4914-88c8-44af-b7fa-fd43cd3bedd5" xlink:href="opk-20201231.xsd#opk_AccruedClinicalTrialsCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_opk_AccruedClinicalTrialsCurrent_5a5c4914-88c8-44af-b7fa-fd43cd3bedd5" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedProfessionalFeesCurrent_a3949316-f086-4b0e-8035-d7d05b92508c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedProfessionalFeesCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_AccruedProfessionalFeesCurrent_a3949316-f086-4b0e-8035-d7d05b92508c" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrent_6758b969-adc2-483d-a420-c1b62fb59019" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinanceLeaseLiabilityCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrent_6758b969-adc2-483d-a420-c1b62fb59019" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent_26a74229-61f5-4b7e-be45-8fc4bdec9d6a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityCurrent_26a74229-61f5-4b7e-be45-8fc4bdec9d6a" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_ffd8e8c5-1358-49d0-8143-1993bf3a64ce" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_ffd8e8c5-1358-49d0-8143-1993bf3a64ce" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_f92dadb1-0dbc-499d-93fa-05f3383454a8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrentAbstract_3b6ae0e0-8d9c-4b1b-8b03-aa2b0df079ec" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_f92dadb1-0dbc-499d-93fa-05f3383454a8" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_d1cce2e9-3230-4975-9bf8-7e4c5c932952" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinanceLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_d1cce2e9-3230-4975-9bf8-7e4c5c932952" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrentAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermLineOfCredit_394e6eab-dcb8-4367-bec0-9a725e9faddd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermLineOfCredit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_LongTermLineOfCredit_394e6eab-dcb8-4367-bec0-9a725e9faddd" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_66e857dd-b90f-4620-a76e-1ab68e1abd82" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_66e857dd-b90f-4620-a76e-1ab68e1abd82" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_bde62d1f-6e67-42ec-85a2-521310dcb314" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_bde62d1f-6e67-42ec-85a2-521310dcb314" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_ab8e0147-4a9d-49f2-b34c-b29f03495f86" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinanceLeaseLiabilityNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_FinanceLeaseLiabilityNoncurrent_ab8e0147-4a9d-49f2-b34c-b29f03495f86" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MortgagesAndOtherDebtsPayable_2e0b938a-58e4-449a-b672-aaf8bf9ae28b" xlink:href="opk-20201231.xsd#opk_MortgagesAndOtherDebtsPayable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_opk_MortgagesAndOtherDebtsPayable_2e0b938a-58e4-449a-b672-aaf8bf9ae28b" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesAndDeferredRevenueNoncurrent_7d3621e8-91a1-48d8-93cf-f2f9da23b966" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesAndDeferredRevenueNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_OtherLiabilitiesAndDeferredRevenueNoncurrent_7d3621e8-91a1-48d8-93cf-f2f9da23b966" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_b65eae86-49c3-492f-b9b7-3d5e54de954a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherLiabilitiesNoncurrentAbstract_caf1a44f-5b3a-4767-9214-f2647b960e12" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_b65eae86-49c3-492f-b9b7-3d5e54de954a" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList_0ae376d0-af26-4c77-9714-38437c6a3886" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinanceLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_us-gaap_FinanceLeaseLiabilityNoncurrentStatementOfFinancialPositionExtensibleList_0ae376d0-af26-4c77-9714-38437c6a3886" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfCondensedFinancialStatementsTable_b063b729-18b0-4865-9781-100864469666" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScheduleOfCondensedFinancialStatementsTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_CondensedFinancialStatementsCaptionsLineItems_d6540409-741e-495d-af7a-c1c1de57a898" xlink:to="loc_srt_ScheduleOfCondensedFinancialStatementsTable_b063b729-18b0-4865-9781-100864469666" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92a1796-3674-48c6-8346-78d4e76baca0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ScheduleOfCondensedFinancialStatementsTable_b063b729-18b0-4865-9781-100864469666" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92a1796-3674-48c6-8346-78d4e76baca0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_e92a1796-3674-48c6-8346-78d4e76baca0_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92a1796-3674-48c6-8346-78d4e76baca0" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_e92a1796-3674-48c6-8346-78d4e76baca0_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92a1796-3674-48c6-8346-78d4e76baca0" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MachineryMedicalandOtherEquipmentMember_f5e8f32f-ce8e-4eec-bf45-0d1e041a39c4" xlink:href="opk-20201231.xsd#opk_MachineryMedicalandOtherEquipmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_opk_MachineryMedicalandOtherEquipmentMember_f5e8f32f-ce8e-4eec-bf45-0d1e041a39c4" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_e3f7ba8e-e583-45da-b1a1-96a02595c485" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LeaseholdImprovementsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_e3f7ba8e-e583-45da-b1a1-96a02595c485" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_6242b865-220c-40e3-a4b3-4494ed14c99e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FurnitureAndFixturesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_6242b865-220c-40e3-a4b3-4494ed14c99e" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AutomobilesandAircraftMember_3711c0f9-5606-416b-afb7-5b57a7c605ab" xlink:href="opk-20201231.xsd#opk_AutomobilesandAircraftMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_opk_AutomobilesandAircraftMember_3711c0f9-5606-416b-afb7-5b57a7c605ab" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_de0f0b04-010a-44a1-b796-512370bb9097" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_de0f0b04-010a-44a1-b796-512370bb9097" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BuildingMember_3031db6c-590e-4557-a315-01b8077d5a66" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BuildingMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_BuildingMember_3031db6c-590e-4557-a315-01b8077d5a66" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandMember_69620e0e-b518-4a2c-8519-8df56e925f10" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LandMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_LandMember_69620e0e-b518-4a2c-8519-8df56e925f10" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressMember_8ba2c727-8bac-4dbe-bc07-6cae36e33e7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConstructionInProgressMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_fc79eba1-21ab-48db-91b7-3961171e3d4a" xlink:to="loc_us-gaap_ConstructionInProgressMember_8ba2c727-8bac-4dbe-bc07-6cae36e33e7d" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_ffba9414-25c4-4146-b716-533a95a6ef95" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ScheduleOfCondensedFinancialStatementsTable_b063b729-18b0-4865-9781-100864469666" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_ffba9414-25c4-4146-b716-533a95a6ef95" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_ffba9414-25c4-4146-b716-533a95a6ef95_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_ffba9414-25c4-4146-b716-533a95a6ef95" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_ffba9414-25c4-4146-b716-533a95a6ef95_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_ffba9414-25c4-4146-b716-533a95a6ef95" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRelationshipsMember_9bd56fe9-937c-4323-ad0d-ad1a5823da36" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CustomerRelationshipsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_CustomerRelationshipsMember_9bd56fe9-937c-4323-ad0d-ad1a5823da36" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_2d11213c-0940-4bcb-aa6b-497f7c202623" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TechnologyBasedIntangibleAssetsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_2d11213c-0940-4bcb-aa6b-497f7c202623" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeNamesMember_5f0b254a-751d-479b-9638-3af2d3b2be0f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TradeNamesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_TradeNamesMember_5f0b254a-751d-479b-9638-3af2d3b2be0f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncompeteAgreementsMember_79cb7988-375c-42df-872a-8f5465b0f5f2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NoncompeteAgreementsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_NoncompeteAgreementsMember_79cb7988-375c-42df-872a-8f5465b0f5f2" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicensingAgreementsMember_981a8811-8371-48ee-9c29-66dea82df037" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LicensingAgreementsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_LicensingAgreementsMember_981a8811-8371-48ee-9c29-66dea82df037" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ProductRegistrationsMember_62eed187-35af-4dfb-9473-03305e8f7af3" xlink:href="opk-20201231.xsd#opk_ProductRegistrationsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_opk_ProductRegistrationsMember_62eed187-35af-4dfb-9473-03305e8f7af3" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherIntangibleAssetsMember_c8a9b587-08b9-41b2-9c14-7c81e5077e37" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherIntangibleAssetsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_37296694-2882-4a68-9e4c-a2ef29b65be7" xlink:to="loc_us-gaap_OtherIntangibleAssetsMember_c8a9b587-08b9-41b2-9c14-7c81e5077e37" xlink:type="arc" order="6"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptionsNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsNarrativeDetails" xlink:type="extended" id="ib627ed7e5bf14cc2b95256de5b212e1c_CompositionofCertainFinancialStatementCaptionsNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_f4aec44e-3e34-4e57-81e9-529ac743cb3f" xlink:href="opk-20201231.xsd#opk_SummaryOfSignificantAccountingPoliciesLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_479992ce-4997-472f-a6a0-bbb4af8e6c23" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_f4aec44e-3e34-4e57-81e9-529ac743cb3f" xlink:to="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_479992ce-4997-472f-a6a0-bbb4af8e6c23" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_e2054b37-a56a-41ba-8263-1f495417a169" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_f4aec44e-3e34-4e57-81e9-529ac743cb3f" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_e2054b37-a56a-41ba-8263-1f495417a169" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_b81bca13-89aa-4258-b5a6-a7f0a24d8f89" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillImpairmentLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_f4aec44e-3e34-4e57-81e9-529ac743cb3f" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_b81bca13-89aa-4258-b5a6-a7f0a24d8f89" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SummaryOfSignificantAccountingPoliciesTable_7ed00231-4b0d-4ee0-b784-ba4f2a38c48c" xlink:href="opk-20201231.xsd#opk_SummaryOfSignificantAccountingPoliciesTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesLineItems_f4aec44e-3e34-4e57-81e9-529ac743cb3f" xlink:to="loc_opk_SummaryOfSignificantAccountingPoliciesTable_7ed00231-4b0d-4ee0-b784-ba4f2a38c48c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_101dd2c3-71fe-4091-bcea-1f39029e8611" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_7ed00231-4b0d-4ee0-b784-ba4f2a38c48c" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_101dd2c3-71fe-4091-bcea-1f39029e8611" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_101dd2c3-71fe-4091-bcea-1f39029e8611_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_101dd2c3-71fe-4091-bcea-1f39029e8611" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_101dd2c3-71fe-4091-bcea-1f39029e8611_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_2f63b0b9-8f4a-414e-80ae-05225e3cbdf7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_101dd2c3-71fe-4091-bcea-1f39029e8611" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_2f63b0b9-8f4a-414e-80ae-05225e3cbdf7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_e5fa9c4a-fe0c-4c41-8f17-594985925a72" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_2f63b0b9-8f4a-414e-80ae-05225e3cbdf7" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_e5fa9c4a-fe0c-4c41-8f17-594985925a72" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TrademarksMember_80c9b45e-36e4-4da5-b060-be8c3f22c4cc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TrademarksMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_2f63b0b9-8f4a-414e-80ae-05225e3cbdf7" xlink:to="loc_us-gaap_TrademarksMember_80c9b45e-36e4-4da5-b060-be8c3f22c4cc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_2cf4f6f0-52f2-41d4-badf-7583913d2cf3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_7ed00231-4b0d-4ee0-b784-ba4f2a38c48c" xlink:to="loc_srt_RangeAxis_2cf4f6f0-52f2-41d4-badf-7583913d2cf3" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2cf4f6f0-52f2-41d4-badf-7583913d2cf3_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_2cf4f6f0-52f2-41d4-badf-7583913d2cf3" xlink:to="loc_srt_RangeMember_2cf4f6f0-52f2-41d4-badf-7583913d2cf3_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9b995606-6a98-4693-809a-ef23ceaafb4c" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_2cf4f6f0-52f2-41d4-badf-7583913d2cf3" xlink:to="loc_srt_RangeMember_9b995606-6a98-4693-809a-ef23ceaafb4c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_4af2da95-e27b-4d04-bd0b-569899688764" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_9b995606-6a98-4693-809a-ef23ceaafb4c" xlink:to="loc_srt_MinimumMember_4af2da95-e27b-4d04-bd0b-569899688764" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_fd16aa4d-7794-4078-93b2-6fea22eec9c2" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_9b995606-6a98-4693-809a-ef23ceaafb4c" xlink:to="loc_srt_MaximumMember_fd16aa4d-7794-4078-93b2-6fea22eec9c2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_3c8d0f88-3926-4fa9-829f-985a492b2252" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_SummaryOfSignificantAccountingPoliciesTable_7ed00231-4b0d-4ee0-b784-ba4f2a38c48c" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_3c8d0f88-3926-4fa9-829f-985a492b2252" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_3c8d0f88-3926-4fa9-829f-985a492b2252_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_3c8d0f88-3926-4fa9-829f-985a492b2252" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_3c8d0f88-3926-4fa9-829f-985a492b2252_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_3c8d0f88-3926-4fa9-829f-985a492b2252" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_20fe5e6b-723a-4456-85b5-377972304a84" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_20fe5e6b-723a-4456-85b5-377972304a84" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DevelopedTechnologyRightsMember_7215bf10-e033-4c3c-9f96-3cd3238f5790" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DevelopedTechnologyRightsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_DevelopedTechnologyRightsMember_7215bf10-e033-4c3c-9f96-3cd3238f5790" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRelationshipsMember_d6890801-c59b-4efe-86a9-58edff89a0f8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CustomerRelationshipsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_CustomerRelationshipsMember_d6890801-c59b-4efe-86a9-58edff89a0f8" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_cc291b38-5cf6-489a-8961-065decfe8e27" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_ProductMember_cc291b38-5cf6-489a-8961-065decfe8e27" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CovenantsNotToCompeteMember_31feaaa8-43db-4493-b893-561bdc8b82e4" xlink:href="opk-20201231.xsd#opk_CovenantsNotToCompeteMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_opk_CovenantsNotToCompeteMember_31feaaa8-43db-4493-b893-561bdc8b82e4" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeNamesMember_6b9df769-afb0-4c8e-9407-8eca0ea7e8e9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TradeNamesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_TradeNamesMember_6b9df769-afb0-4c8e-9407-8eca0ea7e8e9" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherIntangibleAssetsMember_42387fc0-9ec7-4cb6-8976-6067260726e4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherIntangibleAssetsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_d21acc30-a772-42a1-b433-8ec1628e9c66" xlink:to="loc_us-gaap_OtherIntangibleAssetsMember_42387fc0-9ec7-4cb6-8976-6067260726e4" xlink:type="arc" order="6"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsSummaryofValuationAllowanceDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptionsSummaryofValuationAllowanceDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsSummaryofValuationAllowanceDetails" xlink:type="extended" id="i0af04bdbe9204f548448fc81101151ca_CompositionofCertainFinancialStatementCaptionsSummaryofValuationAllowanceDetails">
<link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_065d591b-657b-4e4c-926e-4ae36e836c5b" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_cbb32c43-8f69-43f1-8708-470778dc5e8f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MovementInValuationAllowancesAndReservesRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_065d591b-657b-4e4c-926e-4ae36e836c5b" xlink:to="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_cbb32c43-8f69-43f1-8708-470778dc5e8f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_3fce7f3a-efbf-411e-9cba-e1f6dd8c3400" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_cbb32c43-8f69-43f1-8708-470778dc5e8f" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesBalance_3fce7f3a-efbf-411e-9cba-e1f6dd8c3400" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_2dc29c58-a29f-49d6-877e-e1d74b661600" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_cbb32c43-8f69-43f1-8708-470778dc5e8f" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_2dc29c58-a29f-49d6-877e-e1d74b661600" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDeductions_ab9424d7-f694-44d3-91f8-5b16b897fbc2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDeductions"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MovementInValuationAllowancesAndReservesRollForward_cbb32c43-8f69-43f1-8708-470778dc5e8f" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDeductions_ab9424d7-f694-44d3-91f8-5b16b897fbc2" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_96ee40b8-82f0-4768-b420-8199f02b923b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_e29e8b6e-dbef-4aff-a66c-5d26382b84f9" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_065d591b-657b-4e4c-926e-4ae36e836c5b" xlink:to="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_e29e8b6e-dbef-4aff-a66c-5d26382b84f9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_daf9b78d-3a98-41ec-93e3-1c2546199765" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_e29e8b6e-dbef-4aff-a66c-5d26382b84f9" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_daf9b78d-3a98-41ec-93e3-1c2546199765" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_daf9b78d-3a98-41ec-93e3-1c2546199765_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_daf9b78d-3a98-41ec-93e3-1c2546199765" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_daf9b78d-3a98-41ec-93e3-1c2546199765_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_d327734b-0680-4f92-bf56-a6285dfd5e7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_daf9b78d-3a98-41ec-93e3-1c2546199765" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_d327734b-0680-4f92-bf56-a6285dfd5e7d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForCreditLossMember_897b0d90-2493-4c51-bf98-8332d0266eee" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForCreditLossMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_d327734b-0680-4f92-bf56-a6285dfd5e7d" xlink:to="loc_us-gaap_AllowanceForCreditLossMember_897b0d90-2493-4c51-bf98-8332d0266eee" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryValuationReserveMember_bf6dd11a-c9b7-4631-a54d-d171b5e882f3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InventoryValuationReserveMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_d327734b-0680-4f92-bf56-a6285dfd5e7d" xlink:to="loc_us-gaap_InventoryValuationReserveMember_bf6dd11a-c9b7-4631-a54d-d171b5e882f3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowanceOfDeferredTaxAssetsMember_4c4c4a23-abf6-4a7d-89ae-f78a91272a62" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowanceOfDeferredTaxAssetsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_d327734b-0680-4f92-bf56-a6285dfd5e7d" xlink:to="loc_us-gaap_ValuationAllowanceOfDeferredTaxAssetsMember_4c4c4a23-abf6-4a7d-89ae-f78a91272a62" xlink:type="arc" order="2"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsChangesinGoodwillDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#CompositionofCertainFinancialStatementCaptionsChangesinGoodwillDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CompositionofCertainFinancialStatementCaptionsChangesinGoodwillDetails" xlink:type="extended" id="i07e80f5200ce4ca0910064590211913e_CompositionofCertainFinancialStatementCaptionsChangesinGoodwillDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillLineItems_513cdc5d-0839-421b-b2a0-11cfec584f74" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GoodwillLineItems_513cdc5d-0839-421b-b2a0-11cfec584f74" xlink:to="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_45adb472-250b-4fdc-85c2-5dad10faa4c4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Goodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:to="loc_us-gaap_Goodwill_45adb472-250b-4fdc-85c2-5dad10faa4c4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairedAccumulatedImpairmentLoss_6b84f642-1072-4f6f-8604-9b6eb811728d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillImpairedAccumulatedImpairmentLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:to="loc_us-gaap_GoodwillImpairedAccumulatedImpairmentLoss_6b84f642-1072-4f6f-8604-9b6eb811728d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_f5073c12-f6b7-45ce-8862-fa6ea8cb976a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillImpairmentLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_f5073c12-f6b7-45ce-8862-fa6ea8cb976a" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillForeignCurrencyTranslationGainLoss_2f9a3753-3e5d-4da5-b68e-bd92cde69aa5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GoodwillForeignCurrencyTranslationGainLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GoodwillRollForward_a1cf2943-be3d-4641-8681-2840228e3381" xlink:to="loc_us-gaap_GoodwillForeignCurrencyTranslationGainLoss_2f9a3753-3e5d-4da5-b68e-bd92cde69aa5" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_57f6e271-730b-4239-90e2-664e2817562e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Goodwill"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfGoodwillTable_d49d9692-f400-46fd-83b9-305b37b54c0c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfGoodwillTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_GoodwillLineItems_513cdc5d-0839-421b-b2a0-11cfec584f74" xlink:to="loc_us-gaap_ScheduleOfGoodwillTable_d49d9692-f400-46fd-83b9-305b37b54c0c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_e96b0d9c-4156-48b4-8274-1a1cb9f0999e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfGoodwillTable_d49d9692-f400-46fd-83b9-305b37b54c0c" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_e96b0d9c-4156-48b4-8274-1a1cb9f0999e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_e96b0d9c-4156-48b4-8274-1a1cb9f0999e_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_e96b0d9c-4156-48b4-8274-1a1cb9f0999e" xlink:to="loc_us-gaap_SegmentDomain_e96b0d9c-4156-48b4-8274-1a1cb9f0999e_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_aa446931-55df-463a-8a90-194cabff14fc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_e96b0d9c-4156-48b4-8274-1a1cb9f0999e" xlink:to="loc_us-gaap_SegmentDomain_aa446931-55df-463a-8a90-194cabff14fc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PharmaceuticalMember_17575a77-4715-4048-88af-f3109a89baa8" xlink:href="opk-20201231.xsd#opk_PharmaceuticalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_aa446931-55df-463a-8a90-194cabff14fc" xlink:to="loc_opk_PharmaceuticalMember_17575a77-4715-4048-88af-f3109a89baa8" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DiagnosticsMember_6abd26c9-35d6-4afa-8569-1b4620862378" xlink:href="opk-20201231.xsd#opk_DiagnosticsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_aa446931-55df-463a-8a90-194cabff14fc" xlink:to="loc_opk_DiagnosticsMember_6abd26c9-35d6-4afa-8569-1b4620862378" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_9980eb8f-8712-480b-baca-122b42846e69" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfGoodwillTable_d49d9692-f400-46fd-83b9-305b37b54c0c" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_9980eb8f-8712-480b-baca-122b42846e69" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9980eb8f-8712-480b-baca-122b42846e69_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_9980eb8f-8712-480b-baca-122b42846e69" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_9980eb8f-8712-480b-baca-122b42846e69_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_9980eb8f-8712-480b-baca-122b42846e69" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CURNAMember_aca9c0c5-55cf-4e1a-bd03-ed73a97c12be" xlink:href="opk-20201231.xsd#opk_CURNAMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_CURNAMember_aca9c0c5-55cf-4e1a-bd03-ed73a97c12be" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EirGenPharmaLimitedMember_e85c7f7f-0411-487e-a397-710aaecfac02" xlink:href="opk-20201231.xsd#opk_EirGenPharmaLimitedMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_EirGenPharmaLimitedMember_e85c7f7f-0411-487e-a397-710aaecfac02" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_FineTechMember_e9743e02-5eb6-4d8f-b9c7-b16765dbd9e7" xlink:href="opk-20201231.xsd#opk_FineTechMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_FineTechMember_e9743e02-5eb6-4d8f-b9c7-b16765dbd9e7" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PROLORMember_10235067-15a3-4456-91d1-dc836c663c9f" xlink:href="opk-20201231.xsd#opk_PROLORMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_PROLORMember_10235067-15a3-4456-91d1-dc836c663c9f" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OpkoChileMember_0f3789e2-81f2-485f-b24d-eb2123a5dcb6" xlink:href="opk-20201231.xsd#opk_OpkoChileMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_OpkoChileMember_0f3789e2-81f2-485f-b24d-eb2123a5dcb6" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OPKOHealthEuropeMember_c9d10625-b46e-4c52-b657-17dc4c109cc4" xlink:href="opk-20201231.xsd#opk_OPKOHealthEuropeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_OPKOHealthEuropeMember_c9d10625-b46e-4c52-b657-17dc4c109cc4" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OPKOMexicoMember_b592896b-505b-4cb4-ba5b-5ede9d5768cb" xlink:href="opk-20201231.xsd#opk_OPKOMexicoMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_OPKOMexicoMember_b592896b-505b-4cb4-ba5b-5ede9d5768cb" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TransitionTherapeuticsInc.Member_94122762-531a-40f9-8b42-ff5732ede18b" xlink:href="opk-20201231.xsd#opk_TransitionTherapeuticsInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_TransitionTherapeuticsInc.Member_94122762-531a-40f9-8b42-ff5732ede18b" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioReferenceMember_6d579a6d-bb12-4fb3-9383-7a68c2c35855" xlink:href="opk-20201231.xsd#opk_BioReferenceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_BioReferenceMember_6d579a6d-bb12-4fb3-9383-7a68c2c35855" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OpkoDiagnosticsMember_1a9fc8d0-cb52-4724-a01e-d68665c5104b" xlink:href="opk-20201231.xsd#opk_OpkoDiagnosticsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_c22a5b23-2db3-4c50-bc3f-c787d9ae5476" xlink:to="loc_opk_OpkoDiagnosticsMember_1a9fc8d0-cb52-4724-a01e-d68665c5104b" xlink:type="arc" order="9"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/Debt" xlink:type="simple" xlink:href="opk-20201231.xsd#Debt"/>
<link:definitionLink xlink:role="http://www.opko.com/role/Debt" xlink:type="extended" id="id594fac732284b0aab33b330c60b8107_Debt"/>
<link:roleRef roleURI="http://www.opko.com/role/DebtTables" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtTables" xlink:type="extended" id="i1ee6b9a4bcb447d2baee375147e213df_DebtTables"/>
<link:roleRef roleURI="http://www.opko.com/role/DebtScheduleofDebtDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtScheduleofDebtDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtScheduleofDebtDetails" xlink:type="extended" id="id33b3d6218ab49728d35285584c7027e_DebtScheduleofDebtDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_d4445b20-c318-4438-a0c7-6fc5ac7f36c4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_01105920-a562-435a-a85f-909d00eeef3b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d4445b20-c318-4438-a0c7-6fc5ac7f36c4" xlink:to="loc_us-gaap_LongTermDebt_01105920-a562-435a-a85f-909d00eeef3b" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtCurrent_cd57db87-721c-4d2c-b30f-3c916f84bc9a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d4445b20-c318-4438-a0c7-6fc5ac7f36c4" xlink:to="loc_us-gaap_LongTermDebtCurrent_cd57db87-721c-4d2c-b30f-3c916f84bc9a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_a10e9ed5-0ae8-443c-93f9-b7f24c824c03" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d4445b20-c318-4438-a0c7-6fc5ac7f36c4" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_a10e9ed5-0ae8-443c-93f9-b7f24c824c03" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_d4445b20-c318-4438-a0c7-6fc5ac7f36c4" xlink:to="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_3f2bc428-310f-4305-9fdb-26c9f5058276" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:to="loc_us-gaap_DebtInstrumentAxis_3f2bc428-310f-4305-9fdb-26c9f5058276" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_3f2bc428-310f-4305-9fdb-26c9f5058276_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_3f2bc428-310f-4305-9fdb-26c9f5058276" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_3f2bc428-310f-4305-9fdb-26c9f5058276_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_3f2bc428-310f-4305-9fdb-26c9f5058276" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ConvertibleSeniorNotesDue2025Member_b305c349-b8d5-4137-8827-29fe18f6acca" xlink:href="opk-20201231.xsd#opk_ConvertibleSeniorNotesDue2025Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:to="loc_opk_ConvertibleSeniorNotesDue2025Member_b305c349-b8d5-4137-8827-29fe18f6acca" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_A5ConvertibleNotesMember_b1427c5d-c998-4fd7-ab2d-3faaafbc0869" xlink:href="opk-20201231.xsd#opk_A5ConvertibleNotesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:to="loc_opk_A5ConvertibleNotesMember_b1427c5d-c998-4fd7-ab2d-3faaafbc0869" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NotesDueFebruary12033Member_ace69169-fdbd-4011-8b8a-310642489e14" xlink:href="opk-20201231.xsd#opk_NotesDueFebruary12033Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:to="loc_opk_NotesDueFebruary12033Member_ace69169-fdbd-4011-8b8a-310642489e14" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NewCreditAgreementMember_6e69b1f1-2393-4b1e-ba29-f7473e0e9193" xlink:href="opk-20201231.xsd#opk_NewCreditAgreementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d0ee0fa3-ebdb-46e5-8937-e5ebe1e9eb9d" xlink:to="loc_opk_NewCreditAgreementMember_6e69b1f1-2393-4b1e-ba29-f7473e0e9193" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_3df3720a-e2bb-4f61-9e09-5d122821500d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_3df3720a-e2bb-4f61-9e09-5d122821500d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_3df3720a-e2bb-4f61-9e09-5d122821500d_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_3df3720a-e2bb-4f61-9e09-5d122821500d" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_3df3720a-e2bb-4f61-9e09-5d122821500d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_3df3720a-e2bb-4f61-9e09-5d122821500d" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_16a86635-fde1-42dd-8902-29d1da4f763f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:to="loc_us-gaap_ConvertibleDebtMember_16a86635-fde1-42dd-8902-29d1da4f763f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_145b0791-611a-4ec3-81d3-2ab783b952d0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleNotesPayableMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_145b0791-611a-4ec3-81d3-2ab783b952d0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_9436bc15-5308-487a-885a-f0de965b6788" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:to="loc_us-gaap_LineOfCreditMember_9436bc15-5308-487a-885a-f0de965b6788" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayableOtherPayablesMember_74ba0266-2206-4fd3-8607-7f7988ed9c46" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NotesPayableOtherPayablesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_9c45cdd5-1d0f-43da-950c-3cf000b79df3" xlink:to="loc_us-gaap_NotesPayableOtherPayablesMember_74ba0266-2206-4fd3-8607-7f7988ed9c46" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_8d631104-e1b5-4574-a181-59bbd847c6ce" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_8d631104-e1b5-4574-a181-59bbd847c6ce" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_8d631104-e1b5-4574-a181-59bbd847c6ce_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_8d631104-e1b5-4574-a181-59bbd847c6ce" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_8d631104-e1b5-4574-a181-59bbd847c6ce_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_19d705bd-4e56-4373-aa81-6d5bc0a4cec4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_8d631104-e1b5-4574-a181-59bbd847c6ce" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_19d705bd-4e56-4373-aa81-6d5bc0a4cec4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ConvertibleNotesMember_f0a93f1b-41df-46fb-8d73-4e5dfd2012f9" xlink:href="opk-20201231.xsd#opk_ConvertibleNotesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_19d705bd-4e56-4373-aa81-6d5bc0a4cec4" xlink:to="loc_opk_ConvertibleNotesMember_f0a93f1b-41df-46fb-8d73-4e5dfd2012f9" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LineOfCreditAndNotesAndLoansPayableCurrentMember_f80f2cb0-de98-4d52-a24c-896b25686653" xlink:href="opk-20201231.xsd#opk_LineOfCreditAndNotesAndLoansPayableCurrentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_19d705bd-4e56-4373-aa81-6d5bc0a4cec4" xlink:to="loc_opk_LineOfCreditAndNotesAndLoansPayableCurrentMember_f80f2cb0-de98-4d52-a24c-896b25686653" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNoncurrentLiabilitiesMember_c0e6642a-2b1f-4d1a-ade0-839947591adf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNoncurrentLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_19d705bd-4e56-4373-aa81-6d5bc0a4cec4" xlink:to="loc_us-gaap_OtherNoncurrentLiabilitiesMember_c0e6642a-2b1f-4d1a-ade0-839947591adf" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_584c1038-1871-414b-afb7-0777ce100469" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d6e8e48c-ccc2-485e-90a6-3c872b719297" xlink:to="loc_us-gaap_CreditFacilityAxis_584c1038-1871-414b-afb7-0777ce100469" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_584c1038-1871-414b-afb7-0777ce100469_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_584c1038-1871-414b-afb7-0777ce100469" xlink:to="loc_us-gaap_CreditFacilityDomain_584c1038-1871-414b-afb7-0777ce100469_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_d985f4c6-dc98-4b37-924a-ea9e3a938187" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_584c1038-1871-414b-afb7-0777ce100469" xlink:to="loc_us-gaap_CreditFacilityDomain_d985f4c6-dc98-4b37-924a-ea9e3a938187" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevolvingCreditFacilityMember_582024c1-8361-4780-8f0c-5796b070ac6f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevolvingCreditFacilityMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_d985f4c6-dc98-4b37-924a-ea9e3a938187" xlink:to="loc_us-gaap_RevolvingCreditFacilityMember_582024c1-8361-4780-8f0c-5796b070ac6f" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DebtNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtNarrativeDetails" xlink:type="extended" id="i647541149e6b4349b96327dd2c11f3fc_DebtNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_ca37f265-6351-4edb-9b7a-85887dea9b5d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_ca37f265-6351-4edb-9b7a-85887dea9b5d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_13d3b345-dce3-441e-ad69-0059a946e1a8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_13d3b345-dce3-441e-ad69-0059a946e1a8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage_faf09863-2b5a-4252-a5dd-e4355c6c29b4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage_faf09863-2b5a-4252-a5dd-e4355c6c29b4" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_e0c46f01-eeef-443d-87fb-8f447efe4857" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentFaceAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_e0c46f01-eeef-443d-87fb-8f447efe4857" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_4ca3de9f-a940-4e31-99c9-cb04a5a62a9f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_4ca3de9f-a940-4e31-99c9-cb04a5a62a9f" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_3f2456cd-155b-4662-9812-94815095f7e0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_3f2456cd-155b-4662-9812-94815095f7e0" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_dde39795-3274-4e9f-a143-29ef1a5b88fe" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_dde39795-3274-4e9f-a143-29ef1a5b88fe" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_4a2d6a4e-f3ad-44c9-aead-aca5fa02d6af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionRatio1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_4a2d6a4e-f3ad-44c9-aead-aca5fa02d6af" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_3899e92b-a07a-451e-aa2d-fafca1bb2d96" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_3899e92b-a07a-451e-aa2d-fafca1bb2d96" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_491e2663-d800-4d70-9691-12cf577ef934" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPricePercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_491e2663-d800-4d70-9691-12cf577ef934" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentConvertibleDebtMaximumSharesIssuable_c72a5995-9f1c-458e-b049-98d60f2f14f5" xlink:href="opk-20201231.xsd#opk_DebtInstrumentConvertibleDebtMaximumSharesIssuable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_opk_DebtInstrumentConvertibleDebtMaximumSharesIssuable_c72a5995-9f1c-458e-b049-98d60f2f14f5" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_cc553151-76a2-4124-92a8-2676cd4a101c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_cc553151-76a2-4124-92a8-2676cd4a101c" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_a1d113eb-4da5-4f75-881f-2a1ea32db52e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LongTermDebt_a1d113eb-4da5-4f75-881f-2a1ea32db52e" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ProceedsFromConvertibleDebtConversionFee_9ef097ed-c258-4e09-a0f6-317c1ae44995" xlink:href="opk-20201231.xsd#opk_ProceedsFromConvertibleDebtConversionFee"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_opk_ProceedsFromConvertibleDebtConversionFee_9ef097ed-c258-4e09-a0f6-317c1ae44995" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent_a6eea89a-c660-4c24-affb-87aeac422e24" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentConvertibleCarryingAmountOfTheEquityComponent_a6eea89a-c660-4c24-affb-87aeac422e24" xlink:type="arc" order="14"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_729350b5-9d68-4b60-be70-6c02493dffe3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_729350b5-9d68-4b60-be70-6c02493dffe3" xlink:type="arc" order="15"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLinesOfCredit_aaacb2f8-9062-4072-a0b0-7d5e79409108" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RepaymentsOfLinesOfCredit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_RepaymentsOfLinesOfCredit_aaacb2f8-9062-4072-a0b0-7d5e79409108" xlink:type="arc" order="16"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTerm_d56859d4-6a5a-471c-be03-4d3ee805c7bd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTerm"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentTerm_d56859d4-6a5a-471c-be03-4d3ee805c7bd" xlink:type="arc" order="17"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentConvertibleConversionNoticeThresholdMinimum_a14ea8ef-8c88-4e2b-b620-60c6aae656b1" xlink:href="opk-20201231.xsd#opk_DebtInstrumentConvertibleConversionNoticeThresholdMinimum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_opk_DebtInstrumentConvertibleConversionNoticeThresholdMinimum_a14ea8ef-8c88-4e2b-b620-60c6aae656b1" xlink:type="arc" order="18"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentConvertibleConversionNoticeThresholdMaximum_56256f2d-57d9-4347-8f57-c5fc4c0394cc" xlink:href="opk-20201231.xsd#opk_DebtInstrumentConvertibleConversionNoticeThresholdMaximum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_opk_DebtInstrumentConvertibleConversionNoticeThresholdMaximum_56256f2d-57d9-4347-8f57-c5fc4c0394cc" xlink:type="arc" order="19"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_cfd704ee-97ea-41f5-af93-544a9552ad62" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtConversionConvertedInstrumentAmount1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentAmount1_cfd704ee-97ea-41f5-af93-544a9552ad62" xlink:type="arc" order="20"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRepurchaseAmount_66c0991c-fb7a-4a36-a412-ffbc20aaffdd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRepurchaseAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentRepurchaseAmount_66c0991c-fb7a-4a36-a412-ffbc20aaffdd" xlink:type="arc" order="21"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_40badd2a-814f-488e-9a7d-78f07726e4ac" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_40badd2a-814f-488e-9a7d-78f07726e4ac" xlink:type="arc" order="22"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_a6755422-b755-4df6-9a6c-5c987e69c445" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_a6755422-b755-4df6-9a6c-5c987e69c445" xlink:type="arc" order="23"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermLineOfCredit_7acdaed8-6852-41b9-83b8-37ccba856a76" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermLineOfCredit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LongTermLineOfCredit_7acdaed8-6852-41b9-83b8-37ccba856a76" xlink:type="arc" order="24"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_5a12425d-511b-4f96-8c15-9b040f71f08e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_StockholdersEquity_5a12425d-511b-4f96-8c15-9b040f71f08e" xlink:type="arc" order="25"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_9b74d6cb-c15e-4cd6-a58a-1fa80362e6aa" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Goodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_Goodwill_9b74d6cb-c15e-4cd6-a58a-1fa80362e6aa" xlink:type="arc" order="26"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_56997007-c858-43c0-a9d4-25a0cf17748a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_IntangibleAssetsNetExcludingGoodwill_56997007-c858-43c0-a9d4-25a0cf17748a" xlink:type="arc" order="27"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentsNumberofFinancialInstitutions_46bf8bc0-d616-4541-a75b-d0c2935f2eae" xlink:href="opk-20201231.xsd#opk_DebtInstrumentsNumberofFinancialInstitutions"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_opk_DebtInstrumentsNumberofFinancialInstitutions_46bf8bc0-d616-4541-a75b-d0c2935f2eae" xlink:type="arc" order="28"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtWeightedAverageInterestRate_1f6cafdb-8f14-484e-96a0-24a3a8ec9ccb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtWeightedAverageInterestRate"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtWeightedAverageInterestRate_1f6cafdb-8f14-484e-96a0-24a3a8ec9ccb" xlink:type="arc" order="29"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtPercentageBearingVariableInterestRate_296d9940-a1e1-48d2-8709-38d58d49df2c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtPercentageBearingVariableInterestRate"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_LongTermDebtPercentageBearingVariableInterestRate_296d9940-a1e1-48d2-8709-38d58d49df2c" xlink:type="arc" order="30"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c1af207a-fd9b-4eab-bead-cbc3dc4553f5" xlink:to="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61ca84d4-6ad6-452d-9889-45ffd882510a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61ca84d4-6ad6-452d-9889-45ffd882510a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_61ca84d4-6ad6-452d-9889-45ffd882510a_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61ca84d4-6ad6-452d-9889-45ffd882510a" xlink:to="loc_us-gaap_RelatedPartyDomain_61ca84d4-6ad6-452d-9889-45ffd882510a_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_26fd2d7a-d594-486b-a89b-667338c4cab2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61ca84d4-6ad6-452d-9889-45ffd882510a" xlink:to="loc_us-gaap_RelatedPartyDomain_26fd2d7a-d594-486b-a89b-667338c4cab2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DrFrostMember_fda18300-be43-41f6-b8a3-0c0f79fd2cdf" xlink:href="opk-20201231.xsd#opk_DrFrostMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_26fd2d7a-d594-486b-a89b-667338c4cab2" xlink:to="loc_opk_DrFrostMember_fda18300-be43-41f6-b8a3-0c0f79fd2cdf" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateAxis_3df13529-9d1f-491d-8498-6173f2148df9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_VariableRateAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_VariableRateAxis_3df13529-9d1f-491d-8498-6173f2148df9" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_3df13529-9d1f-491d-8498-6173f2148df9_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_VariableRateDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VariableRateAxis_3df13529-9d1f-491d-8498-6173f2148df9" xlink:to="loc_us-gaap_VariableRateDomain_3df13529-9d1f-491d-8498-6173f2148df9_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_VariableRateDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VariableRateAxis_3df13529-9d1f-491d-8498-6173f2148df9" xlink:to="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LondonInterbankOfferedRateLIBORMember_bf32b99b-acd5-489e-b8b7-8db6364c5e74" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LondonInterbankOfferedRateLIBORMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:to="loc_us-gaap_LondonInterbankOfferedRateLIBORMember_bf32b99b-acd5-489e-b8b7-8db6364c5e74" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsMember_0ea700e6-f526-4f6d-bd82-e2a84ea7b4c6" xlink:href="opk-20201231.xsd#opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:to="loc_opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsMember_0ea700e6-f526-4f6d-bd82-e2a84ea7b4c6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LondonInterbankOfferedRateLIBORThereafterMember_a0fd4885-931f-4188-9bce-8980d8fd9b4f" xlink:href="opk-20201231.xsd#opk_LondonInterbankOfferedRateLIBORThereafterMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:to="loc_opk_LondonInterbankOfferedRateLIBORThereafterMember_a0fd4885-931f-4188-9bce-8980d8fd9b4f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsAdjustedforEurocurrencyLiabilitiesMember_e320cd14-1bc6-488b-bf32-27a36f81dcc4" xlink:href="opk-20201231.xsd#opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsAdjustedforEurocurrencyLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:to="loc_opk_LondonInterbankOfferedRateLIBORFirstTwelveMonthsAdjustedforEurocurrencyLiabilitiesMember_e320cd14-1bc6-488b-bf32-27a36f81dcc4" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LondonInterbankOfferedRateLIBORThereafterAdjustedforEurocurrencyLiabilitiesMember_0fb0ae4f-4ef3-4293-86c2-9226286879f3" xlink:href="opk-20201231.xsd#opk_LondonInterbankOfferedRateLIBORThereafterAdjustedforEurocurrencyLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_17f8e7cb-f0fa-4940-88d8-e3d2e32c6005" xlink:to="loc_opk_LondonInterbankOfferedRateLIBORThereafterAdjustedforEurocurrencyLiabilitiesMember_0fb0ae4f-4ef3-4293-86c2-9226286879f3" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_80424d32-2880-4785-9cd7-1acb33ff345b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_CreditFacilityAxis_80424d32-2880-4785-9cd7-1acb33ff345b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_80424d32-2880-4785-9cd7-1acb33ff345b_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_80424d32-2880-4785-9cd7-1acb33ff345b" xlink:to="loc_us-gaap_CreditFacilityDomain_80424d32-2880-4785-9cd7-1acb33ff345b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_80424d32-2880-4785-9cd7-1acb33ff345b" xlink:to="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_45139d70-36bc-4fca-a08c-f95be83bc5c1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:to="loc_us-gaap_LineOfCreditMember_45139d70-36bc-4fca-a08c-f95be83bc5c1" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevolvingCreditFacilityMember_9c9ac505-66df-45ec-a51d-fb8b892353e4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevolvingCreditFacilityMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:to="loc_us-gaap_RevolvingCreditFacilityMember_9c9ac505-66df-45ec-a51d-fb8b892353e4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BridgeLoanMember_abc458aa-55e7-4104-bfa1-1fe390a91518" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BridgeLoanMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:to="loc_us-gaap_BridgeLoanMember_abc458aa-55e7-4104-bfa1-1fe390a91518" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LetterOfCreditMember_54243ef0-8ea0-491a-b27e-718b1c66f874" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LetterOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_1ff54e3c-cac1-43dd-9123-b9e5a2dd73af" xlink:to="loc_us-gaap_LetterOfCreditMember_54243ef0-8ea0-491a-b27e-718b1c66f874" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_StatementClassOfStockAxis_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638" xlink:to="loc_us-gaap_ClassOfStockDomain_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_24d39f66-f63b-43b9-9d21-bbfcccb30bef" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_ca8b8771-6e9a-4f6b-9ef3-f9a657a88638" xlink:to="loc_us-gaap_ClassOfStockDomain_24d39f66-f63b-43b9-9d21-bbfcccb30bef" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_098d6577-42b1-4c37-80a5-ba13764dc076" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_24d39f66-f63b-43b9-9d21-bbfcccb30bef" xlink:to="loc_us-gaap_CommonStockMember_098d6577-42b1-4c37-80a5-ba13764dc076" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_82b52832-4450-400b-842e-e5e5da88a524" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_82b52832-4450-400b-842e-e5e5da88a524" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_82b52832-4450-400b-842e-e5e5da88a524_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_82b52832-4450-400b-842e-e5e5da88a524" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_82b52832-4450-400b-842e-e5e5da88a524_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_82b52832-4450-400b-842e-e5e5da88a524" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_f1cdeb33-5cc0-4059-bcfc-df1a65ad7d03" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:to="loc_us-gaap_LineOfCreditMember_f1cdeb33-5cc0-4059-bcfc-df1a65ad7d03" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnsecuredDebtMember_8aadab7e-a973-4f49-a59d-a72f44f19184" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnsecuredDebtMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:to="loc_us-gaap_UnsecuredDebtMember_8aadab7e-a973-4f49-a59d-a72f44f19184" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_24e83bad-d2e0-4a82-a8e9-33e52b847c2b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:to="loc_us-gaap_ConvertibleDebtMember_24e83bad-d2e0-4a82-a8e9-33e52b847c2b" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_0eb529f7-288a-4bd9-99c8-fb7f40e13772" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleNotesPayableMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_53678401-0e2d-441d-9847-26755725a91d" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_0eb529f7-288a-4bd9-99c8-fb7f40e13772" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_DebtInstrumentAxis_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_3d9ba2c2-2bd5-4a16-afd8-2b3cdc39fbbf" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ConvertibleSeniorNotesDue2025Member_bf1df028-725e-4752-8860-26225a96a91f" xlink:href="opk-20201231.xsd#opk_ConvertibleSeniorNotesDue2025Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:to="loc_opk_ConvertibleSeniorNotesDue2025Member_bf1df028-725e-4752-8860-26225a96a91f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_A5ConvertibleNotesMember_8f03fb2f-5faf-4619-89a9-3e7969260007" xlink:href="opk-20201231.xsd#opk_A5ConvertibleNotesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:to="loc_opk_A5ConvertibleNotesMember_8f03fb2f-5faf-4619-89a9-3e7969260007" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NotesDueFebruary12033Member_91d077d0-0b2f-4bc2-a52f-5d193eeaf411" xlink:href="opk-20201231.xsd#opk_NotesDueFebruary12033Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:to="loc_opk_NotesDueFebruary12033Member_91d077d0-0b2f-4bc2-a52f-5d193eeaf411" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NewCreditAgreementMember_df4eb562-0d0e-42a8-a250-3ad5721fe676" xlink:href="opk-20201231.xsd#opk_NewCreditAgreementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_f88e3082-ec81-4cf6-a11a-0fd3d981a6de" xlink:to="loc_opk_NewCreditAgreementMember_df4eb562-0d0e-42a8-a250-3ad5721fe676" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_e7973dae-c53d-4ed6-b5d9-c396bc1f0463" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_e7973dae-c53d-4ed6-b5d9-c396bc1f0463" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_e7973dae-c53d-4ed6-b5d9-c396bc1f0463_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_e7973dae-c53d-4ed6-b5d9-c396bc1f0463" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_e7973dae-c53d-4ed6-b5d9-c396bc1f0463_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1b38e69b-7f13-4d5e-8fe7-6450835b1251" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_e7973dae-c53d-4ed6-b5d9-c396bc1f0463" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1b38e69b-7f13-4d5e-8fe7-6450835b1251" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_a5e03d0b-0b14-4379-9171-14387df89414" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodOneMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1b38e69b-7f13-4d5e-8fe7-6450835b1251" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_a5e03d0b-0b14-4379-9171-14387df89414" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_1220da7c-3997-426e-831a-287e57f61690" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodTwoMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1b38e69b-7f13-4d5e-8fe7-6450835b1251" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodTwoMember_1220da7c-3997-426e-831a-287e57f61690" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodThreeMember_17a7f922-2a67-4ee2-a096-d29a66027922" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRedemptionPeriodThreeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_1b38e69b-7f13-4d5e-8fe7-6450835b1251" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodThreeMember_17a7f922-2a67-4ee2-a096-d29a66027922" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_d8611a16-fbb0-4abd-8042-adb25b039a20" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_srt_RangeAxis_d8611a16-fbb0-4abd-8042-adb25b039a20" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_d8611a16-fbb0-4abd-8042-adb25b039a20_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_d8611a16-fbb0-4abd-8042-adb25b039a20" xlink:to="loc_srt_RangeMember_d8611a16-fbb0-4abd-8042-adb25b039a20_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_62a8b84e-5af4-47df-b98d-6d5121666c73" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_d8611a16-fbb0-4abd-8042-adb25b039a20" xlink:to="loc_srt_RangeMember_62a8b84e-5af4-47df-b98d-6d5121666c73" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_c56199aa-0c76-429a-92e0-4cd0c11f0e28" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_62a8b84e-5af4-47df-b98d-6d5121666c73" xlink:to="loc_srt_MinimumMember_c56199aa-0c76-429a-92e0-4cd0c11f0e28" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_af071ce0-aa1f-47d6-b725-8a5f693afbb1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_62a8b84e-5af4-47df-b98d-6d5121666c73" xlink:to="loc_srt_MaximumMember_af071ce0-aa1f-47d6-b725-8a5f693afbb1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_c8179d7c-fc35-4139-8b28-f79cc9ac673c" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_124856c4-fa05-4917-8ac9-c6a87fd3b5ae" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_054990d8-7627-4ef1-a6ac-d5f0e0ed39a0" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_124856c4-fa05-4917-8ac9-c6a87fd3b5ae" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioReferenceMember_8ff06706-688f-4260-bde4-b083c753e18b" xlink:href="opk-20201231.xsd#opk_BioReferenceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_124856c4-fa05-4917-8ac9-c6a87fd3b5ae" xlink:to="loc_opk_BioReferenceMember_8ff06706-688f-4260-bde4-b083c753e18b" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OPKOHealthEuropeMember_1279a800-4b20-4495-83ce-be71b386416f" xlink:href="opk-20201231.xsd#opk_OPKOHealthEuropeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_124856c4-fa05-4917-8ac9-c6a87fd3b5ae" xlink:to="loc_opk_OPKOHealthEuropeMember_1279a800-4b20-4495-83ce-be71b386416f" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DebtScheduleofNotesDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtScheduleofNotesDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtScheduleofNotesDetails" xlink:type="extended" id="i65ce489e01c547ec86823c86a22c0ced_DebtScheduleofNotesDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_b797772a-846b-458a-8ced-6ea04f84e794" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:href="opk-20201231.xsd#opk_DebtInstrumentRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_b797772a-846b-458a-8ced-6ea04f84e794" xlink:to="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeniorLongtermNotesCurrentAndNoncurrentAbstract_de37f4c2-80ee-4cef-b581-62affa4e5829" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeniorLongtermNotesCurrentAndNoncurrentAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:to="loc_us-gaap_SeniorLongtermNotesCurrentAndNoncurrentAbstract_de37f4c2-80ee-4cef-b581-62affa4e5829" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_5e4cc86c-f30b-4157-b929-341c43bf8b8c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SeniorLongtermNotesCurrentAndNoncurrentAbstract_de37f4c2-80ee-4cef-b581-62affa4e5829" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_5e4cc86c-f30b-4157-b929-341c43bf8b8c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_a80dd8c6-9500-4ee1-a524-0b1d31ad9c1a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountAbstract_d139caff-2e58-49a4-97d2-aaaf5c0b1cb6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscountAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountAbstract_d139caff-2e58-49a4-97d2-aaaf5c0b1cb6" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscount_d87e2158-5508-4ff3-a0ca-df93dd078e02" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentUnamortizedDiscountAbstract_d139caff-2e58-49a4-97d2-aaaf5c0b1cb6" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscount_d87e2158-5508-4ff3-a0ca-df93dd078e02" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfDebtDiscountPremium_ac9ff582-6b3a-4557-901d-e5da79e24672" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentUnamortizedDiscountAbstract_d139caff-2e58-49a4-97d2-aaaf5c0b1cb6" xlink:to="loc_us-gaap_AmortizationOfDebtDiscountPremium_ac9ff582-6b3a-4557-901d-e5da79e24672" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscount_3af5255c-8e05-4d07-8117-3333e11192ee" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscount"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNetAbstract_6c7499e5-607c-4ed2-a862-e7b8959f400e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredFinanceCostsNetAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:to="loc_us-gaap_DeferredFinanceCostsNetAbstract_6c7499e5-607c-4ed2-a862-e7b8959f400e" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_3dd63e11-cc91-4ef8-aa03-1f7a9435bb07" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredFinanceCostsNet"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DeferredFinanceCostsNetAbstract_6c7499e5-607c-4ed2-a862-e7b8959f400e" xlink:to="loc_us-gaap_DeferredFinanceCostsNet_3dd63e11-cc91-4ef8-aa03-1f7a9435bb07" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_76a6178b-4bc7-41e7-9ce3-a76097dac4b2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfFinancingCosts"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DeferredFinanceCostsNetAbstract_6c7499e5-607c-4ed2-a862-e7b8959f400e" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_76a6178b-4bc7-41e7-9ce3-a76097dac4b2" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_5d8610c7-4b45-4c88-a9bd-148940d56e71" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredFinanceCostsNet"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtAbstract_48d84394-8792-464a-b836-ae60cdb36fb7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_DebtInstrumentRollForward_6225cad1-37c6-4108-b8f1-c1b6a97b5d6a" xlink:to="loc_us-gaap_LongTermDebtAbstract_48d84394-8792-464a-b836-ae60cdb36fb7" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_0bfc6eeb-ec4b-49fd-aad2-168415544f42" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermDebtAbstract_48d84394-8792-464a-b836-ae60cdb36fb7" xlink:to="loc_us-gaap_LongTermDebt_0bfc6eeb-ec4b-49fd-aad2-168415544f42" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_38c9b78c-9400-4c91-8e5f-5fd12376b33d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermDebtAbstract_48d84394-8792-464a-b836-ae60cdb36fb7" xlink:to="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_38c9b78c-9400-4c91-8e5f-5fd12376b33d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_d449544c-b9fb-4bb9-9706-4117fd442ada" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_d9c5d8c6-b61f-45db-96d7-82837517a8ad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_b797772a-846b-458a-8ced-6ea04f84e794" xlink:to="loc_us-gaap_DebtInstrumentTable_d9c5d8c6-b61f-45db-96d7-82837517a8ad" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_0f567eac-2466-4adc-87d3-84ad8df1496e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_d9c5d8c6-b61f-45db-96d7-82837517a8ad" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_0f567eac-2466-4adc-87d3-84ad8df1496e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_0f567eac-2466-4adc-87d3-84ad8df1496e_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_0f567eac-2466-4adc-87d3-84ad8df1496e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_0f567eac-2466-4adc-87d3-84ad8df1496e_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_0c21bae4-7d21-4e1f-83b7-c84d7c194aad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_0f567eac-2466-4adc-87d3-84ad8df1496e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_0c21bae4-7d21-4e1f-83b7-c84d7c194aad" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeniorNotesMember_1b74df43-ef77-40e5-9d36-bfce7b6c01f0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeniorNotesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_0c21bae4-7d21-4e1f-83b7-c84d7c194aad" xlink:to="loc_us-gaap_SeniorNotesMember_1b74df43-ef77-40e5-9d36-bfce7b6c01f0" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DebtSummaryofLinesofCreditDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtSummaryofLinesofCreditDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtSummaryofLinesofCreditDetails" xlink:type="extended" id="ie719bade0b3f402297f5433264b16a24_DebtSummaryofLinesofCreditDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_3f119de0-c927-48b3-a726-cbc5dae10c4b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityInterestRateAtPeriodEnd_cb465086-0fe6-4646-b3be-d22e3b768e4d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityInterestRateAtPeriodEnd"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_3f119de0-c927-48b3-a726-cbc5dae10c4b" xlink:to="loc_us-gaap_LineOfCreditFacilityInterestRateAtPeriodEnd_cb465086-0fe6-4646-b3be-d22e3b768e4d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_731370bd-f05d-4925-b5fb-d87ece308fc7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_3f119de0-c927-48b3-a726-cbc5dae10c4b" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_731370bd-f05d-4925-b5fb-d87ece308fc7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_485d16c5-28db-4ed2-8ee8-c09250ea465c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCredit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_3f119de0-c927-48b3-a726-cbc5dae10c4b" xlink:to="loc_us-gaap_LineOfCredit_485d16c5-28db-4ed2-8ee8-c09250ea465c" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_34478817-8a85-462b-bbb2-cfd2dabe1823" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_3f119de0-c927-48b3-a726-cbc5dae10c4b" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_34478817-8a85-462b-bbb2-cfd2dabe1823" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_f761b1f5-1643-403c-8a55-f9a06702d22c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_34478817-8a85-462b-bbb2-cfd2dabe1823" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_f761b1f5-1643-403c-8a55-f9a06702d22c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_f761b1f5-1643-403c-8a55-f9a06702d22c_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_f761b1f5-1643-403c-8a55-f9a06702d22c" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_f761b1f5-1643-403c-8a55-f9a06702d22c_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_f761b1f5-1643-403c-8a55-f9a06702d22c" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_JPMorganChaseMember_75ad82b6-07b3-42e0-82f5-df7b76ba0230" xlink:href="opk-20201231.xsd#opk_JPMorganChaseMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_JPMorganChaseMember_75ad82b6-07b3-42e0-82f5-df7b76ba0230" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ItauBankMember_536e88e5-04f2-4337-9e7f-5658b106557a" xlink:href="opk-20201231.xsd#opk_ItauBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_ItauBankMember_536e88e5-04f2-4337-9e7f-5658b106557a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BankOfChileMember_d751698e-9e29-4b77-a984-530978a1e422" xlink:href="opk-20201231.xsd#opk_BankOfChileMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_BankOfChileMember_d751698e-9e29-4b77-a984-530978a1e422" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BiceBankMember_e38757f1-bce1-42ff-a782-79298517086a" xlink:href="opk-20201231.xsd#opk_BiceBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_BiceBankMember_e38757f1-bce1-42ff-a782-79298517086a" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BbvaBankMember_b1e419cd-5019-4f7b-ad27-f9b48439778a" xlink:href="opk-20201231.xsd#opk_BbvaBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_BbvaBankMember_b1e419cd-5019-4f7b-ad27-f9b48439778a" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SecurityMember_97970f1e-96e8-46bb-bc80-0a5ab193b570" xlink:href="opk-20201231.xsd#opk_SecurityMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_SecurityMember_97970f1e-96e8-46bb-bc80-0a5ab193b570" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EstadoBankMember_8c17b322-6332-4119-9f85-1ac34bc7c8aa" xlink:href="opk-20201231.xsd#opk_EstadoBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_EstadoBankMember_8c17b322-6332-4119-9f85-1ac34bc7c8aa" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SabadellBankMember_4c632bd7-ebb7-402c-964d-06dc3bc8a1f0" xlink:href="opk-20201231.xsd#opk_SabadellBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_SabadellBankMember_4c632bd7-ebb7-402c-964d-06dc3bc8a1f0" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ScotiabankMember_4d841f00-32de-4466-9a93-f457a01deeef" xlink:href="opk-20201231.xsd#opk_ScotiabankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_ScotiabankMember_4d841f00-32de-4466-9a93-f457a01deeef" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CorpbancaMember_87e64c11-b840-4466-b1bd-a05299973c49" xlink:href="opk-20201231.xsd#opk_CorpbancaMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_CorpbancaMember_87e64c11-b840-4466-b1bd-a05299973c49" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BancoDeSabadellMember_475323f5-0d81-460d-b087-cedac7ff7dd2" xlink:href="opk-20201231.xsd#opk_BancoDeSabadellMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_BancoDeSabadellMember_475323f5-0d81-460d-b087-cedac7ff7dd2" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BilbaoVizcayaBankMember_a0688b17-f321-4a2b-97c2-2be330fdb553" xlink:href="opk-20201231.xsd#opk_BilbaoVizcayaBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_BilbaoVizcayaBankMember_a0688b17-f321-4a2b-97c2-2be330fdb553" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SantanderBankMember_97510c0d-bef1-4a05-9962-809c331302f3" xlink:href="opk-20201231.xsd#opk_SantanderBankMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_2ff0d3e1-3bc9-435b-9994-b0aaf78fa482" xlink:to="loc_opk_SantanderBankMember_97510c0d-bef1-4a05-9962-809c331302f3" xlink:type="arc" order="12"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DebtMortgageNotesandOtherDebtDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DebtMortgageNotesandOtherDebtDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DebtMortgageNotesandOtherDebtDetails" xlink:type="extended" id="i6a2e151c6f39492caeeb0c1a2c3956e5_DebtMortgageNotesandOtherDebtDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_60eaac9f-a7be-4093-baf0-a12917f76b57" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract_12fcc9f2-120b-477c-9b35-d14ad6dae7f7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_60eaac9f-a7be-4093-baf0-a12917f76b57" xlink:to="loc_us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract_12fcc9f2-120b-477c-9b35-d14ad6dae7f7" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtCurrent_9b80b8ab-b1e1-43ee-bef9-60efe5996ae4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtCurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract_12fcc9f2-120b-477c-9b35-d14ad6dae7f7" xlink:to="loc_us-gaap_LongTermDebtCurrent_9b80b8ab-b1e1-43ee-bef9-60efe5996ae4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_70dc2985-b132-4c4f-8f74-66e1c6bc4668" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtNoncurrent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract_12fcc9f2-120b-477c-9b35-d14ad6dae7f7" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_70dc2985-b132-4c4f-8f74-66e1c6bc4668" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_f51c4d25-c0a6-487b-9143-75a590f1a107" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongTermDebtByCurrentAndNoncurrentAbstract_12fcc9f2-120b-477c-9b35-d14ad6dae7f7" xlink:to="loc_us-gaap_LongTermDebt_f51c4d25-c0a6-487b-9143-75a590f1a107" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_bb23e5ac-3eda-49ee-be58-da478ac7ea8b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_60eaac9f-a7be-4093-baf0-a12917f76b57" xlink:to="loc_us-gaap_DebtInstrumentTable_bb23e5ac-3eda-49ee-be58-da478ac7ea8b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_fb2aef20-1983-4695-a4ef-b56e70af5cdc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_bb23e5ac-3eda-49ee-be58-da478ac7ea8b" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_fb2aef20-1983-4695-a4ef-b56e70af5cdc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_fb2aef20-1983-4695-a4ef-b56e70af5cdc_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_fb2aef20-1983-4695-a4ef-b56e70af5cdc" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_fb2aef20-1983-4695-a4ef-b56e70af5cdc_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_3f7ec4c7-0d40-4008-bd89-76ae6578c13a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_fb2aef20-1983-4695-a4ef-b56e70af5cdc" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_3f7ec4c7-0d40-4008-bd89-76ae6578c13a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NotesPayableAndOtherLongTermLiabilitiesMember_3d4c4293-d4ed-4eb0-b676-7d14ddb09f63" xlink:href="opk-20201231.xsd#opk_NotesPayableAndOtherLongTermLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_3f7ec4c7-0d40-4008-bd89-76ae6578c13a" xlink:to="loc_opk_NotesPayableAndOtherLongTermLiabilitiesMember_3d4c4293-d4ed-4eb0-b676-7d14ddb09f63" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/ShareholdersEquity" xlink:type="simple" xlink:href="opk-20201231.xsd#ShareholdersEquity"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ShareholdersEquity" xlink:type="extended" id="i9472c63b20fc48ab82fd59ce01b4103e_ShareholdersEquity"/>
<link:roleRef roleURI="http://www.opko.com/role/ShareholdersEquityNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#ShareholdersEquityNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/ShareholdersEquityNarrativeDetails" xlink:type="extended" id="i4ad14d4e7b4945a1b5a8a1050a926d02_ShareholdersEquityNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_146f459c-a17f-4535-9bac-fe160f22838c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockSharesAuthorized"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_146f459c-a17f-4535-9bac-fe160f22838c" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_e616f228-150a-47b2-a37e-1c746f2a68c2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_e616f228-150a-47b2-a37e-1c746f2a68c2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_49cc203f-4fed-4c70-96b2-82c18eb58787" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockSharesAuthorized"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_49cc203f-4fed-4c70-96b2-82c18eb58787" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_b1c59fc5-b494-4eaf-961d-c244d6e58b9b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_b1c59fc5-b494-4eaf-961d-c244d6e58b9b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_29609525-07b2-4bdd-ac65-c17740e75ed9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_29609525-07b2-4bdd-ac65-c17740e75ed9" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_0face9f4-9e3e-404a-b6af-718a9c58f0ee" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_0face9f4-9e3e-404a-b6af-718a9c58f0ee" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_c9520a8e-f80e-485a-a817-0b768a383dad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_c9520a8e-f80e-485a-a817-0b768a383dad" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesShares_9b8ff4de-1b6c-4664-a6cf-6ec6345871d3" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesShares"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesShares_9b8ff4de-1b6c-4664-a6cf-6ec6345871d3" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesPricePerShare_b92b7afd-369b-4621-9a8f-aa560bb0f634" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesPricePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesPricePerShare_b92b7afd-369b-4621-9a8f-aa560bb0f634" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesAmount_374ef196-32ef-4bce-b197-ff2c6349d6d7" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesAmount_374ef196-32ef-4bce-b197-ff2c6349d6d7" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CommonStockVotingRightsVotesPerShare_9197fcc6-8362-4214-869a-1650171ef986" xlink:href="opk-20201231.xsd#opk_CommonStockVotingRightsVotesPerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_opk_CommonStockVotingRightsVotesPerShare_9197fcc6-8362-4214-869a-1650171ef986" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ConvertiblePreferredStockSharesDesignatedMaximum_ab5f98d4-4b7a-4b10-80cd-1913c19987cd" xlink:href="opk-20201231.xsd#opk_ConvertiblePreferredStockSharesDesignatedMaximum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_opk_ConvertiblePreferredStockSharesDesignatedMaximum_ab5f98d4-4b7a-4b10-80cd-1913c19987cd" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_a22d67af-b770-4266-858b-63c2ca1b955f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockSharesIssued"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_PreferredStockSharesIssued_a22d67af-b770-4266-858b-63c2ca1b955f" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_fbf1553d-c49f-497f-81f6-89e460223efe" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockSharesOutstanding"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_fbf1553d-c49f-497f-81f6-89e460223efe" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfStockByClassTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_4d29c1a8-7c9e-4b76-84e6-6f87ddf21a7c" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_52b535eb-8b91-45eb-8ac2-2501ca31ebc8" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CounterpartyNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:to="loc_srt_CounterpartyNameAxis_52b535eb-8b91-45eb-8ac2-2501ca31ebc8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_52b535eb-8b91-45eb-8ac2-2501ca31ebc8_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_52b535eb-8b91-45eb-8ac2-2501ca31ebc8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_52b535eb-8b91-45eb-8ac2-2501ca31ebc8_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_83769c39-eec9-4dd8-a21a-8e117a8ab311" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_52b535eb-8b91-45eb-8ac2-2501ca31ebc8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_83769c39-eec9-4dd8-a21a-8e117a8ab311" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MembersofSeniorManagementMember_4fd2507a-1540-42d4-bafc-21625fc9300f" xlink:href="opk-20201231.xsd#opk_MembersofSeniorManagementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_83769c39-eec9-4dd8-a21a-8e117a8ab311" xlink:to="loc_opk_MembersofSeniorManagementMember_4fd2507a-1540-42d4-bafc-21625fc9300f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_04c18380-fa80-4fc4-aa4f-b1f36d315a87" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_43a66c3c-2a56-4b3a-ac9e-3050e4ed459b" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_04c18380-fa80-4fc4-aa4f-b1f36d315a87" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IPOMember_8f781221-2d25-481a-a18c-7bb231d8ea9b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IPOMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_04c18380-fa80-4fc4-aa4f-b1f36d315a87" xlink:to="loc_us-gaap_IPOMember_8f781221-2d25-481a-a18c-7bb231d8ea9b" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OverAllotmentOptionMember_09454402-4a27-4e37-a205-8cb668faa1a3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OverAllotmentOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_04c18380-fa80-4fc4-aa4f-b1f36d315a87" xlink:to="loc_us-gaap_OverAllotmentOptionMember_09454402-4a27-4e37-a205-8cb668faa1a3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_832e456c-b1e7-496d-944c-d6938e0539ac" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:to="loc_srt_TitleOfIndividualAxis_832e456c-b1e7-496d-944c-d6938e0539ac" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_832e456c-b1e7-496d-944c-d6938e0539ac_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_832e456c-b1e7-496d-944c-d6938e0539ac" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_832e456c-b1e7-496d-944c-d6938e0539ac_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_641698b5-d9be-4336-ad70-fdfa34cc571c" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_832e456c-b1e7-496d-944c-d6938e0539ac" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_641698b5-d9be-4336-ad70-fdfa34cc571c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ChiefExecutiveOfficerMember_ecb45e2f-2752-49fb-8e03-e1f7cee0bcb1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ChiefExecutiveOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_641698b5-d9be-4336-ad70-fdfa34cc571c" xlink:to="loc_srt_ChiefExecutiveOfficerMember_ecb45e2f-2752-49fb-8e03-e1f7cee0bcb1" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChiefTechnicalOfficerMember_c78396ce-fe3c-4c4a-a82d-0943e1239a61" xlink:href="opk-20201231.xsd#opk_ChiefTechnicalOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_641698b5-d9be-4336-ad70-fdfa34cc571c" xlink:to="loc_opk_ChiefTechnicalOfficerMember_c78396ce-fe3c-4c4a-a82d-0943e1239a61" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_17a6d865-ca01-4269-a2b9-729c71f90766" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_f64f9d0f-2bd8-4b4e-93b9-31759e9bfa2a" xlink:to="loc_us-gaap_StatementClassOfStockAxis_17a6d865-ca01-4269-a2b9-729c71f90766" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_17a6d865-ca01-4269-a2b9-729c71f90766_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_17a6d865-ca01-4269-a2b9-729c71f90766" xlink:to="loc_us-gaap_ClassOfStockDomain_17a6d865-ca01-4269-a2b9-729c71f90766_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_f22c416c-cfea-4dc3-ad44-9a83fbdfb9c8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_17a6d865-ca01-4269-a2b9-729c71f90766" xlink:to="loc_us-gaap_ClassOfStockDomain_f22c416c-cfea-4dc3-ad44-9a83fbdfb9c8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesAPreferredStockMember_8f89b85b-8fd1-4b28-aef9-55b319d476cb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeriesAPreferredStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_f22c416c-cfea-4dc3-ad44-9a83fbdfb9c8" xlink:to="loc_us-gaap_SeriesAPreferredStockMember_8f89b85b-8fd1-4b28-aef9-55b319d476cb" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_4f03cac9-17b3-4cf2-99dd-250d6d3b5979" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeriesCPreferredStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_f22c416c-cfea-4dc3-ad44-9a83fbdfb9c8" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_4f03cac9-17b3-4cf2-99dd-250d6d3b5979" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesDPreferredStockMember_a7b07ca6-bb2b-4810-b259-a7573a6d8e7c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeriesDPreferredStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_f22c416c-cfea-4dc3-ad44-9a83fbdfb9c8" xlink:to="loc_us-gaap_SeriesDPreferredStockMember_a7b07ca6-bb2b-4810-b259-a7573a6d8e7c" xlink:type="arc" order="2"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLoss" xlink:type="simple" xlink:href="opk-20201231.xsd#AccumulatedOtherComprehensiveIncomeLoss"/>
<link:definitionLink xlink:role="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLoss" xlink:type="extended" id="i2c67455a885541bda3e8e34f9b3f0849_AccumulatedOtherComprehensiveIncomeLoss"/>
<link:roleRef roleURI="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLossTables" xlink:type="simple" xlink:href="opk-20201231.xsd#AccumulatedOtherComprehensiveIncomeLossTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLossTables" xlink:type="extended" id="i00b828377db6476b84a2a8db560791d3_AccumulatedOtherComprehensiveIncomeLossTables"/>
<link:roleRef roleURI="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLossChangesinAccumulatedOtherComprehensiveIncomeNetofTaxDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#AccumulatedOtherComprehensiveIncomeLossChangesinAccumulatedOtherComprehensiveIncomeNetofTaxDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/AccumulatedOtherComprehensiveIncomeLossChangesinAccumulatedOtherComprehensiveIncomeNetofTaxDetails" xlink:type="extended" id="i6f771af3e1844e0b8f8347e13f3269e2_AccumulatedOtherComprehensiveIncomeLossChangesinAccumulatedOtherComprehensiveIncomeNetofTaxDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_f9f2ac9a-5217-4b02-a314-8a47ce9393fe" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_bb028ebd-1d14-4975-bf56-ad123461016e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AOCIAttributableToParentNetOfTaxRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_f9f2ac9a-5217-4b02-a314-8a47ce9393fe" xlink:to="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_bb028ebd-1d14-4975-bf56-ad123461016e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_b0515154-4341-40c1-a37f-0a422fa90cb0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_bb028ebd-1d14-4975-bf56-ad123461016e" xlink:to="loc_us-gaap_StockholdersEquity_b0515154-4341-40c1-a37f-0a422fa90cb0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_e654e709-f2c9-4823-860e-aed37a6a5664" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AOCIAttributableToParentNetOfTaxRollForward_bb028ebd-1d14-4975-bf56-ad123461016e" xlink:to="loc_us-gaap_OciBeforeReclassificationsNetOfTaxAttributableToParent_e654e709-f2c9-4823-860e-aed37a6a5664" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_bf58ea3b-2392-4745-86af-b2672e89b978" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_e970397a-f023-4477-a329-9e00255c10d1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems_f9f2ac9a-5217-4b02-a314-8a47ce9393fe" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_e970397a-f023-4477-a329-9e00255c10d1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_479e89fe-4098-478a-ade7-63b557731430" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossTable_e970397a-f023-4477-a329-9e00255c10d1" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_479e89fe-4098-478a-ade7-63b557731430" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_479e89fe-4098-478a-ade7-63b557731430_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_479e89fe-4098-478a-ade7-63b557731430" xlink:to="loc_us-gaap_EquityComponentDomain_479e89fe-4098-478a-ade7-63b557731430_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_76f092f1-493e-4da1-8254-840099b9f76d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityComponentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_479e89fe-4098-478a-ade7-63b557731430" xlink:to="loc_us-gaap_EquityComponentDomain_76f092f1-493e-4da1-8254-840099b9f76d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedTranslationAdjustmentMember_6da2afca-71ff-49b2-a3fb-4d65581c2695" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedTranslationAdjustmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_76f092f1-493e-4da1-8254-840099b9f76d" xlink:to="loc_us-gaap_AccumulatedTranslationAdjustmentMember_6da2afca-71ff-49b2-a3fb-4d65581c2695" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/EquityBasedCompensation" xlink:type="simple" xlink:href="opk-20201231.xsd#EquityBasedCompensation"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EquityBasedCompensation" xlink:type="extended" id="idb3eb4e5d4754a16b0067ac7751800b9_EquityBasedCompensation"/>
<link:roleRef roleURI="http://www.opko.com/role/EquityBasedCompensationTables" xlink:type="simple" xlink:href="opk-20201231.xsd#EquityBasedCompensationTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EquityBasedCompensationTables" xlink:type="extended" id="ib2cac37b4b934381a4f20cb7f4be646d_EquityBasedCompensationTables"/>
<link:roleRef roleURI="http://www.opko.com/role/EquityBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#EquityBasedCompensationNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EquityBasedCompensationNarrativeDetails" xlink:type="extended" id="i6bcc54ffaeb746fdb33ad4eb707d74e1_EquityBasedCompensationNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NumberOfEquityBasedIncentiveCompensationPlans_8646dbc4-e1d4-4e3b-86ae-a2783ecb25de" xlink:href="opk-20201231.xsd#opk_NumberOfEquityBasedIncentiveCompensationPlans"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_opk_NumberOfEquityBasedIncentiveCompensationPlans_8646dbc4-e1d4-4e3b-86ae-a2783ecb25de" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_955b52e6-dbf2-41fa-8c17-e832e671bc23" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_955b52e6-dbf2-41fa-8c17-e832e671bc23" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_7f646a00-6c22-4c64-90b0-2ced279c3bcf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_7f646a00-6c22-4c64-90b0-2ced279c3bcf" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ExcessTaxBenefitFromShareBasedCompensationOperatingActivities_567380a6-bb12-4c21-9f80-b13a9f5cdf02" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ExcessTaxBenefitFromShareBasedCompensationOperatingActivities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ExcessTaxBenefitFromShareBasedCompensationOperatingActivities_567380a6-bb12-4c21-9f80-b13a9f5cdf02" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_24d07d72-5e2f-45f2-a5a9-f740899a1bb1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_24d07d72-5e2f-45f2-a5a9-f740899a1bb1" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_c2e0048a-4740-48dc-8ad3-5926309b1dcb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_c2e0048a-4740-48dc-8ad3-5926309b1dcb" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_226347b6-c922-4885-9bdb-a112c1e0ffe1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_226347b6-c922-4885-9bdb-a112c1e0ffe1" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_6714b562-815a-490b-ad6a-2b1e88190304" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_6714b562-815a-490b-ad6a-2b1e88190304" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_a2eb637e-dd0a-42b2-8ba6-839037a47b3d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_a2eb637e-dd0a-42b2-8ba6-839037a47b3d" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_89b31e60-9953-49fd-94ac-dc1f776cb806" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_89b31e60-9953-49fd-94ac-dc1f776cb806" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_cb4bb9f8-5fee-404d-914d-63ab6fbef2a7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_cb4bb9f8-5fee-404d-914d-63ab6fbef2a7" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_059408a5-e805-47f0-b039-754388f3cc21" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_059408a5-e805-47f0-b039-754388f3cc21" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2853e757-020c-4eb6-af16-0115fe212161" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_811d8a08-bcf6-4867-bb6d-649a72d964e1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_srt_TitleOfIndividualAxis_811d8a08-bcf6-4867-bb6d-649a72d964e1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_811d8a08-bcf6-4867-bb6d-649a72d964e1_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_811d8a08-bcf6-4867-bb6d-649a72d964e1" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_811d8a08-bcf6-4867-bb6d-649a72d964e1_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_cd0be3c0-b86e-4f35-ad84-764bb683ade1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_811d8a08-bcf6-4867-bb6d-649a72d964e1" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_cd0be3c0-b86e-4f35-ad84-764bb683ade1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NonemployeeDirectorMember_5cf5d274-3aa2-4472-966b-f445ee06019f" xlink:href="opk-20201231.xsd#opk_NonemployeeDirectorMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_cd0be3c0-b86e-4f35-ad84-764bb683ade1" xlink:to="loc_opk_NonemployeeDirectorMember_5cf5d274-3aa2-4472-966b-f445ee06019f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_e9de9668-3afe-467c-9a01-19aba8fa95a9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AwardTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_us-gaap_AwardTypeAxis_e9de9668-3afe-467c-9a01-19aba8fa95a9" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e9de9668-3afe-467c-9a01-19aba8fa95a9_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_e9de9668-3afe-467c-9a01-19aba8fa95a9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e9de9668-3afe-467c-9a01-19aba8fa95a9_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ddfbd1b8-dfbf-414f-878c-ea307e0e5571" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_e9de9668-3afe-467c-9a01-19aba8fa95a9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ddfbd1b8-dfbf-414f-878c-ea307e0e5571" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_f12247cb-3cea-465a-9873-8214659f0f06" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ddfbd1b8-dfbf-414f-878c-ea307e0e5571" xlink:to="loc_us-gaap_EmployeeStockOptionMember_f12247cb-3cea-465a-9873-8214659f0f06" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_d708cccd-e24b-4e32-8560-cc1445bd25b4" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_srt_RangeAxis_d708cccd-e24b-4e32-8560-cc1445bd25b4" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_d708cccd-e24b-4e32-8560-cc1445bd25b4_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_d708cccd-e24b-4e32-8560-cc1445bd25b4" xlink:to="loc_srt_RangeMember_d708cccd-e24b-4e32-8560-cc1445bd25b4_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_1689eb55-3329-48bc-90b5-bfd3b9100454" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_d708cccd-e24b-4e32-8560-cc1445bd25b4" xlink:to="loc_srt_RangeMember_1689eb55-3329-48bc-90b5-bfd3b9100454" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_5d58a675-ce68-4860-9a22-bb46d1fcbd7e" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_1689eb55-3329-48bc-90b5-bfd3b9100454" xlink:to="loc_srt_MinimumMember_5d58a675-ce68-4860-9a22-bb46d1fcbd7e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_9e26f5a1-ff95-496d-b08c-d1587173e5bd" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_1689eb55-3329-48bc-90b5-bfd3b9100454" xlink:to="loc_srt_MaximumMember_9e26f5a1-ff95-496d-b08c-d1587173e5bd" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOperatingActivitiesSegmentAxis_794963f3-358d-4c1f-8eb0-3523177f3063" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementOperatingActivitiesSegmentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_us-gaap_StatementOperatingActivitiesSegmentAxis_794963f3-358d-4c1f-8eb0-3523177f3063" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentOperatingActivitiesDomain_794963f3-358d-4c1f-8eb0-3523177f3063_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentOperatingActivitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementOperatingActivitiesSegmentAxis_794963f3-358d-4c1f-8eb0-3523177f3063" xlink:to="loc_us-gaap_SegmentOperatingActivitiesDomain_794963f3-358d-4c1f-8eb0-3523177f3063_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentOperatingActivitiesDomain_c3ab3b19-302f-4661-9f8d-5c63b19e38b3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentOperatingActivitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementOperatingActivitiesSegmentAxis_794963f3-358d-4c1f-8eb0-3523177f3063" xlink:to="loc_us-gaap_SegmentOperatingActivitiesDomain_c3ab3b19-302f-4661-9f8d-5c63b19e38b3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentContinuingOperationsMember_3e29230c-0810-4f7a-9c41-bc78f328f825" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentContinuingOperationsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentOperatingActivitiesDomain_c3ab3b19-302f-4661-9f8d-5c63b19e38b3" xlink:to="loc_us-gaap_SegmentContinuingOperationsMember_3e29230c-0810-4f7a-9c41-bc78f328f825" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PlanNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_us-gaap_PlanNameAxis_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f" xlink:to="loc_us-gaap_PlanNameDomain_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_157adf53-d46d-4b66-86bb-609581052fb7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_84d8559d-0ff8-4e68-95ce-02c0ab6bfe2f" xlink:to="loc_us-gaap_PlanNameDomain_157adf53-d46d-4b66-86bb-609581052fb7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TwoThousandSevenEquityIncentivePlanMember_b1c8b06c-2c66-4dbf-8d4b-228074534976" xlink:href="opk-20201231.xsd#opk_TwoThousandSevenEquityIncentivePlanMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_157adf53-d46d-4b66-86bb-609581052fb7" xlink:to="loc_opk_TwoThousandSevenEquityIncentivePlanMember_b1c8b06c-2c66-4dbf-8d4b-228074534976" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_b2f528f6-75bf-43c9-a5da-43037187d37b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_5f1d205d-e069-4aa2-86e7-aa49f6340cc1" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_b2f528f6-75bf-43c9-a5da-43037187d37b" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_b2f528f6-75bf-43c9-a5da-43037187d37b_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_b2f528f6-75bf-43c9-a5da-43037187d37b" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_b2f528f6-75bf-43c9-a5da-43037187d37b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_03a86354-fbd1-40de-8a34-e8beca5f4526" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_b2f528f6-75bf-43c9-a5da-43037187d37b" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_03a86354-fbd1-40de-8a34-e8beca5f4526" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_08de10ee-4aeb-4edb-9146-7e94e959974d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_03a86354-fbd1-40de-8a34-e8beca5f4526" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_08de10ee-4aeb-4edb-9146-7e94e959974d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_2a980c63-bac2-42d2-99a2-8aa5ca5e949e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_03a86354-fbd1-40de-8a34-e8beca5f4526" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_2a980c63-bac2-42d2-99a2-8aa5ca5e949e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfSalesMember_9f180f39-2647-4da7-9fcc-dadeb542a220" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CostOfSalesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_03a86354-fbd1-40de-8a34-e8beca5f4526" xlink:to="loc_us-gaap_CostOfSalesMember_9f180f39-2647-4da7-9fcc-dadeb542a220" xlink:type="arc" order="2"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/EquityBasedCompensationSummaryofOptionPricingFormulaDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#EquityBasedCompensationSummaryofOptionPricingFormulaDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EquityBasedCompensationSummaryofOptionPricingFormulaDetails" xlink:type="extended" id="if4939462764c48d3bd21beba4c5f2e51_EquityBasedCompensationSummaryofOptionPricingFormulaDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57662df8-9e0c-432f-b8f2-06f8120265eb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57662df8-9e0c-432f-b8f2-06f8120265eb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_6c1845bd-f227-46e7-a8cd-afe5ca169409" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_6c1845bd-f227-46e7-a8cd-afe5ca169409" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_b2e376b5-5f1e-4439-9a64-9e85a0d33b6d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_b2e376b5-5f1e-4439-9a64-9e85a0d33b6d" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_1a06bc17-0db5-4adf-8598-48f91fe58ca5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_1a06bc17-0db5-4adf-8598-48f91fe58ca5" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_ffe7e9c8-a4ea-4d42-a577-50a3e0568916" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_ffe7e9c8-a4ea-4d42-a577-50a3e0568916" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_036d4feb-cee5-49b1-bedb-3f2cd0ea3a7a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_036d4feb-cee5-49b1-bedb-3f2cd0ea3a7a" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_2c1e8eb9-0a07-43a9-aae5-691d318704f4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_47b52343-0a16-4904-9053-3384cbc98e48" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_2c1e8eb9-0a07-43a9-aae5-691d318704f4" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_1cc7c9ae-aabe-4641-b41a-fe398d57744e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_57662df8-9e0c-432f-b8f2-06f8120265eb" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_1cc7c9ae-aabe-4641-b41a-fe398d57744e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b247bb4e-4287-4ae9-a830-9004acc782e6" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_1cc7c9ae-aabe-4641-b41a-fe398d57744e" xlink:to="loc_srt_RangeAxis_b247bb4e-4287-4ae9-a830-9004acc782e6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b247bb4e-4287-4ae9-a830-9004acc782e6_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b247bb4e-4287-4ae9-a830-9004acc782e6" xlink:to="loc_srt_RangeMember_b247bb4e-4287-4ae9-a830-9004acc782e6_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_dc2d9e8c-2c71-40e1-a8d2-b5036785a693" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b247bb4e-4287-4ae9-a830-9004acc782e6" xlink:to="loc_srt_RangeMember_dc2d9e8c-2c71-40e1-a8d2-b5036785a693" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_62878560-e4f7-4319-a4b0-3af117039464" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_dc2d9e8c-2c71-40e1-a8d2-b5036785a693" xlink:to="loc_srt_MinimumMember_62878560-e4f7-4319-a4b0-3af117039464" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_b8f2d8cb-9117-4ce1-bc82-a5b2c61cc0f3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_dc2d9e8c-2c71-40e1-a8d2-b5036785a693" xlink:to="loc_srt_MaximumMember_b8f2d8cb-9117-4ce1-bc82-a5b2c61cc0f3" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/EquityBasedCompensationSummaryofOptionActivityDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#EquityBasedCompensationSummaryofOptionActivityDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EquityBasedCompensationSummaryofOptionActivityDetails" xlink:type="extended" id="if216d450b2004dc38f3178bf58d62cf1_EquityBasedCompensationSummaryofOptionActivityDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxes" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxes"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxes" xlink:type="extended" id="i71bf165baf6349f1804e64cd0c5b15a0_IncomeTaxes"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesTables" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesTables" xlink:type="extended" id="id9d8ee96694f4c20b8a90dfd0ac1a26e_IncomeTaxesTables"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesComponentsofIncomeTaxBenefitProvisionDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesComponentsofIncomeTaxBenefitProvisionDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesComponentsofIncomeTaxBenefitProvisionDetails" xlink:type="extended" id="idfd3fb11ce23499d86d8ac82a761a577_IncomeTaxesComponentsofIncomeTaxBenefitProvisionDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesComponentsofDeferredIncomeTaxAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesComponentsofDeferredIncomeTaxAssetsandLiabilitiesDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesComponentsofDeferredIncomeTaxAssetsandLiabilitiesDetails" xlink:type="extended" id="if06e3b0839854108922e801b1a8575d5_IncomeTaxesComponentsofDeferredIncomeTaxAssetsandLiabilitiesDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsLineItems_33fd3762-dcc8-498a-9d5d-4f4b6ec9e82e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwardsLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_33fd3762-dcc8-498a-9d5d-4f4b6ec9e82e" xlink:to="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComponentsOfDeferredTaxAssetsAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:to="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic_649890b4-c271-414f-be2e-4e353525258d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsDomestic_649890b4-c271-414f-be2e-4e353525258d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsStateAndLocal_5c996a26-a5ae-45e4-9cf9-368b0348a724" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsStateAndLocal"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsStateAndLocal_5c996a26-a5ae-45e4-9cf9-368b0348a724" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsForeign_b03e84a3-a07e-4d29-ad94-8f61d4b464ed" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsForeign"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsForeign_b03e84a3-a07e-4d29-ad94-8f61d4b464ed" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment_d109f6cb-7ab7-4e2a-9be0-82a1131cd4f3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsInProcessResearchAndDevelopment_d109f6cb-7ab7-4e2a-9be0-82a1131cd4f3" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_760e7083-6c42-4412-8d77-f6b792f5ac52" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsResearch_760e7083-6c42-4412-8d77-f6b792f5ac52" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_d30a14a9-91c2-44a7-83a6-1d77786062bc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost_d30a14a9-91c2-44a7-83a6-1d77786062bc" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities_37cc4793-b1f5-440f-85b8-92c6bd1035b4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilities_37cc4793-b1f5-440f-85b8-92c6bd1035b4" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsEquityMethodInvestments_fd6132e8-01f8-48fe-a841-e280cbb58b0b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsEquityMethodInvestments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsEquityMethodInvestments_fd6132e8-01f8-48fe-a841-e280cbb58b0b" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAllowanceForDoubtfulAccounts_86e2ce7c-ccd2-4849-8e0d-8cd70938292a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAllowanceForDoubtfulAccounts"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAllowanceForDoubtfulAccounts_86e2ce7c-ccd2-4849-8e0d-8cd70938292a" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent_eef4c407-01c5-453b-83fd-e7423c92e260" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsDeferredRent_eef4c407-01c5-453b-83fd-e7423c92e260" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsForeign_948b2d0e-a5db-4596-8bd7-2c69ac86ea39" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsForeign"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsTaxCreditCarryforwardsForeign_948b2d0e-a5db-4596-8bd7-2c69ac86ea39" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsUnrealizedLossesOnAvailableforSaleSecuritiesGross_cc1c5b0a-bdd3-4c57-be5e-582bff8d40e5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsUnrealizedLossesOnAvailableforSaleSecuritiesGross"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsUnrealizedLossesOnAvailableforSaleSecuritiesGross_cc1c5b0a-bdd3-4c57-be5e-582bff8d40e5" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DeferredTaxAssetsOperatingLeaseAsset_f2302767-2fb3-4b98-a8bf-5822e88c9bb2" xlink:href="opk-20201231.xsd#opk_DeferredTaxAssetsOperatingLeaseAsset"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_opk_DeferredTaxAssetsOperatingLeaseAsset_f2302767-2fb3-4b98-a8bf-5822e88c9bb2" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOtherTaxCarryforwards_f3ca5bc2-098d-4278-b99b-597e4a11f803" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsOtherTaxCarryforwards"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsOtherTaxCarryforwards_f3ca5bc2-098d-4278-b99b-597e4a11f803" xlink:type="arc" order="14"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsGross_3e5c9fea-4d36-45e2-88fe-99743849359c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsGross"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAbstract_2394e03f-807f-429f-b757-54871eb3d0e4" xlink:to="loc_us-gaap_DeferredTaxAssetsGross_3e5c9fea-4d36-45e2-88fe-99743849359c" xlink:type="arc" order="15"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:to="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssetsIntangibleAssets_35bc5708-e191-498e-9873-6c32852de7ee" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssetsIntangibleAssets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_us-gaap_DeferredTaxLiabilitiesGoodwillAndIntangibleAssetsIntangibleAssets_35bc5708-e191-498e-9873-6c32852de7ee" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DeferredTaxLiabilitiesConvertibleDebt_daa4b5ed-6ce6-4c28-be51-dc7c7c35f25c" xlink:href="opk-20201231.xsd#opk_DeferredTaxLiabilitiesConvertibleDebt"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_opk_DeferredTaxLiabilitiesConvertibleDebt_daa4b5ed-6ce6-4c28-be51-dc7c7c35f25c" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilitiesLeasingArrangements_2b7bc207-6a6a-48f9-8596-d6f9b5e1e21b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxLiabilitiesLeasingArrangements"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_us-gaap_DeferredTaxLiabilitiesLeasingArrangements_2b7bc207-6a6a-48f9-8596-d6f9b5e1e21b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_b557eb59-5d31-498b-a6e9-ee6de0a3bda7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment_b557eb59-5d31-498b-a6e9-ee6de0a3bda7" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilitiesOther_edbf179d-2e64-4568-8d25-2ff44a1838a3" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxLiabilitiesOther"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_us-gaap_DeferredTaxLiabilitiesOther_edbf179d-2e64-4568-8d25-2ff44a1838a3" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilities_6ac3201b-441c-494e-aa53-3cf225306d89" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredIncomeTaxLiabilities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxLiabilitiesAbstract_b63302ae-c3fe-468d-b191-3179add528c5" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilities_6ac3201b-441c-494e-aa53-3cf225306d89" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DeferredTaxLiabilitiesNetBeforeValuationAllowance_572eee27-a139-4b3c-ac38-1942e79a7126" xlink:href="opk-20201231.xsd#opk_DeferredTaxLiabilitiesNetBeforeValuationAllowance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:to="loc_opk_DeferredTaxLiabilitiesNetBeforeValuationAllowance_572eee27-a139-4b3c-ac38-1942e79a7126" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsValuationAllowance_c9a56760-92dc-45c1-b583-0b3bded34cbd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetsValuationAllowance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:to="loc_us-gaap_DeferredTaxAssetsValuationAllowance_c9a56760-92dc-45c1-b583-0b3bded34cbd" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxLiabilities_be25cfd4-e6d6-47fb-b14c-6947a6ae6f83" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxLiabilities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ComponentsOfDeferredTaxAssetsAndLiabilitiesAbstract_dd13a001-c07a-47f0-acc6-baff3a4032d1" xlink:to="loc_us-gaap_DeferredTaxLiabilities_be25cfd4-e6d6-47fb-b14c-6947a6ae6f83" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_305eb9e5-4874-4a9a-80bf-ca2ab14d2b6c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_33fd3762-dcc8-498a-9d5d-4f4b6ec9e82e" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_305eb9e5-4874-4a9a-80bf-ca2ab14d2b6c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_7ef795bb-29c2-4867-9bef-64ee6d8a95a6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_305eb9e5-4874-4a9a-80bf-ca2ab14d2b6c" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_7ef795bb-29c2-4867-9bef-64ee6d8a95a6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_7ef795bb-29c2-4867-9bef-64ee6d8a95a6_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_7ef795bb-29c2-4867-9bef-64ee6d8a95a6" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_7ef795bb-29c2-4867-9bef-64ee6d8a95a6_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_f458b986-5901-4bda-91a1-5664ef2b6bf9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_7ef795bb-29c2-4867-9bef-64ee6d8a95a6" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_f458b986-5901-4bda-91a1-5664ef2b6bf9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsMember_690e5711-f0c1-455c-a5ce-c3215d7f2a7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_f458b986-5901-4bda-91a1-5664ef2b6bf9" xlink:to="loc_us-gaap_OtherAssetsMember_690e5711-f0c1-455c-a5ce-c3215d7f2a7d" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesNarrativeDetails" xlink:type="extended" id="i734837b5ea1d4e5c9d8e093808a5548d_IncomeTaxesNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwardsLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwards_a6aa48dd-19b3-44ed-9a85-160986f16ae4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwards"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_OperatingLossCarryforwards_a6aa48dd-19b3-44ed-9a85-160986f16ae4" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardAmount_685a1c96-cdd0-429d-9148-5473d5ed3de5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TaxCreditCarryforwardAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_TaxCreditCarryforwardAmount_685a1c96-cdd0-429d-9148-5473d5ed3de5" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetIntraEntityTransferAssetOtherThanInventory_44c147b8-c675-4a66-9d39-4e268da7af94" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DeferredTaxAssetIntraEntityTransferAssetOtherThanInventory"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_DeferredTaxAssetIntraEntityTransferAssetOtherThanInventory_44c147b8-c675-4a66-9d39-4e268da7af94" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TaxCreditCarryforwardExpirationPeriod_d9d6b675-1c17-4879-a0b9-d9aef9faf74c" xlink:href="opk-20201231.xsd#opk_TaxCreditCarryforwardExpirationPeriod"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_opk_TaxCreditCarryforwardExpirationPeriod_d9d6b675-1c17-4879-a0b9-d9aef9faf74c" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsValuationAllowance_5bb5ceb9-7d93-4f05-a8eb-715a80eb9431" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwardsValuationAllowance"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_OperatingLossCarryforwardsValuationAllowance_5bb5ceb9-7d93-4f05-a8eb-715a80eb9431" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefits_56f80b15-317f-4a2b-a346-78e6e84e0924" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnrecognizedTaxBenefits"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_UnrecognizedTaxBenefits_56f80b15-317f-4a2b-a346-78e6e84e0924" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_72cfe67d-16c6-4972-8043-6694922f43ff" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_72cfe67d-16c6-4972-8043-6694922f43ff" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_e1105747-079f-43e8-ad3b-bf25400f63db" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_e1105747-079f-43e8-ad3b-bf25400f63db" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SignificantChangeInUnrecognizedTaxBenefitsIsReasonablyPossibleAmountOfUnrecordedBenefit_5234b1d7-8c3e-45ab-b7a8-6065d8664c37" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SignificantChangeInUnrecognizedTaxBenefitsIsReasonablyPossibleAmountOfUnrecordedBenefit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_SignificantChangeInUnrecognizedTaxBenefitsIsReasonablyPossibleAmountOfUnrecordedBenefit_5234b1d7-8c3e-45ab-b7a8-6065d8664c37" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_8f1f7d88-b42c-4792-91a9-0c9c5399c989" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d8891d1-c5c4-423e-9867-c75c9300a18f" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_8f1f7d88-b42c-4792-91a9-0c9c5399c989" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_8f1f7d88-b42c-4792-91a9-0c9c5399c989" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_d49b063a-e721-4a9b-b48c-d1b78324b3a2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_3a1ccafc-f12d-4efd-bbc6-e38a0bdc7452" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_d49b063a-e721-4a9b-b48c-d1b78324b3a2" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_57a3c872-3072-4888-8520-5d38345d7712" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DomesticCountryMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_d49b063a-e721-4a9b-b48c-d1b78324b3a2" xlink:to="loc_us-gaap_DomesticCountryMember_57a3c872-3072-4888-8520-5d38345d7712" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalJurisdictionMember_a312382f-57ed-457f-a450-fa78e010bcc1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StateAndLocalJurisdictionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_d49b063a-e721-4a9b-b48c-d1b78324b3a2" xlink:to="loc_us-gaap_StateAndLocalJurisdictionMember_a312382f-57ed-457f-a450-fa78e010bcc1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignCountryMember_309b88f6-9a1c-4211-b302-26d93c90c687" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForeignCountryMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_d49b063a-e721-4a9b-b48c-d1b78324b3a2" xlink:to="loc_us-gaap_ForeignCountryMember_309b88f6-9a1c-4211-b302-26d93c90c687" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardAxis_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TaxCreditCarryforwardAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_8f1f7d88-b42c-4792-91a9-0c9c5399c989" xlink:to="loc_us-gaap_TaxCreditCarryforwardAxis_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardNameDomain_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TaxCreditCarryforwardNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TaxCreditCarryforwardAxis_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4" xlink:to="loc_us-gaap_TaxCreditCarryforwardNameDomain_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardNameDomain_653f9563-f888-4209-bda3-1a9ceeeb7d79" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TaxCreditCarryforwardNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TaxCreditCarryforwardAxis_e8c96a48-1ca7-4003-98ac-a7f4dfb6efa4" xlink:to="loc_us-gaap_TaxCreditCarryforwardNameDomain_653f9563-f888-4209-bda3-1a9ceeeb7d79" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchMember_486131db-276e-4ab0-b4f1-b10b95fd166e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TaxCreditCarryforwardNameDomain_653f9563-f888-4209-bda3-1a9ceeeb7d79" xlink:to="loc_us-gaap_ResearchMember_486131db-276e-4ab0-b4f1-b10b95fd166e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b1ace199-e765-4613-9f55-32a516621ae5" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_8f1f7d88-b42c-4792-91a9-0c9c5399c989" xlink:to="loc_srt_RangeAxis_b1ace199-e765-4613-9f55-32a516621ae5" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b1ace199-e765-4613-9f55-32a516621ae5_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b1ace199-e765-4613-9f55-32a516621ae5" xlink:to="loc_srt_RangeMember_b1ace199-e765-4613-9f55-32a516621ae5_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a3dd13d9-49a9-4c4b-9045-2f90610bc544" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b1ace199-e765-4613-9f55-32a516621ae5" xlink:to="loc_srt_RangeMember_a3dd13d9-49a9-4c4b-9045-2f90610bc544" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_39827d19-1f37-439e-858f-6bc86bae2197" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a3dd13d9-49a9-4c4b-9045-2f90610bc544" xlink:to="loc_srt_MinimumMember_39827d19-1f37-439e-858f-6bc86bae2197" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_9b280729-263a-4f96-9c1f-d615bc92c38e" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a3dd13d9-49a9-4c4b-9045-2f90610bc544" xlink:to="loc_srt_MaximumMember_9b280729-263a-4f96-9c1f-d615bc92c38e" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesChangeinGrossUnrecognizedIncomeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesChangeinGrossUnrecognizedIncomeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesChangeinGrossUnrecognizedIncomeDetails" xlink:type="extended" id="i9b1672415dc647e9afe9a9afcf4c14c5_IncomeTaxesChangeinGrossUnrecognizedIncomeDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesScheduleofDifferenceinFederalandEffectiveTaxRateDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesScheduleofDifferenceinFederalandEffectiveTaxRateDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesScheduleofDifferenceinFederalandEffectiveTaxRateDetails" xlink:type="extended" id="ie241dbecc60e4d4fafb7f0c6b49ec873_IncomeTaxesScheduleofDifferenceinFederalandEffectiveTaxRateDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/IncomeTaxesReconciliationLossesBeforeTaxUSandForeignJurisdictionsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#IncomeTaxesReconciliationLossesBeforeTaxUSandForeignJurisdictionsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/IncomeTaxesReconciliationLossesBeforeTaxUSandForeignJurisdictionsDetails" xlink:type="extended" id="id3a38919a63647c48f7868415233e97e_IncomeTaxesReconciliationLossesBeforeTaxUSandForeignJurisdictionsDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/RelatedPartyTransactions" xlink:type="simple" xlink:href="opk-20201231.xsd#RelatedPartyTransactions"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RelatedPartyTransactions" xlink:type="extended" id="ic60d3edcea364d299f0035be4664a8d9_RelatedPartyTransactions"/>
<link:roleRef roleURI="http://www.opko.com/role/RelatedPartyTransactionsNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#RelatedPartyTransactionsNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RelatedPartyTransactionsNarrativeDetails" xlink:type="extended" id="i1755ad8d3f464126b1555be9c2290b93_RelatedPartyTransactionsNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_911dc3ae-0e86-42f0-a43b-5d29c149b42d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionAmountsOfTransaction"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_911dc3ae-0e86-42f0-a43b-5d29c149b42d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireEquityMethodInvestments_2e8e2d53-b357-48a9-9b29-e26bc3cf0717" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireEquityMethodInvestments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_PaymentsToAcquireEquityMethodInvestments_2e8e2d53-b357-48a9-9b29-e26bc3cf0717" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_4e4c3b9b-8f39-4f6a-991e-5d666ee051bc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_4e4c3b9b-8f39-4f6a-991e-5d666ee051bc" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_f0844cfc-c0f0-4226-ae48-189a81667527" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_f0844cfc-c0f0-4226-ae48-189a81667527" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_cb62a39e-5f52-451c-a7ff-7a9093b3db22" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_cb62a39e-5f52-451c-a7ff-7a9093b3db22" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage_ebee5d7b-abcb-4799-a512-72f688881d60" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_LineOfCreditFacilityUnusedCapacityCommitmentFeePercentage_ebee5d7b-abcb-4799-a512-72f688881d60" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_76b0e471-a700-40b2-bcb8-ad21350fba20" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_76b0e471-a700-40b2-bcb8-ad21350fba20" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_2594c3d1-bf77-47c6-a438-a232a8b51465" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_2594c3d1-bf77-47c6-a438-a232a8b51465" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_66308bf5-7e49-4149-9a0a-2e3a60c7c27a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_66308bf5-7e49-4149-9a0a-2e3a60c7c27a" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_13614b8a-acca-4100-8345-abce569fab82" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SharesIssued"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_SharesIssued_13614b8a-acca-4100-8345-abce569fab82" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RelatedPartyTransactionShares_8caab4b6-4d56-4487-ab06-05c6f85731af" xlink:href="opk-20201231.xsd#opk_RelatedPartyTransactionShares"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_RelatedPartyTransactionShares_8caab4b6-4d56-4487-ab06-05c6f85731af" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesShares_12bc72d6-2e5a-4cd2-94d4-14e5c9ad49fa" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesShares"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesShares_12bc72d6-2e5a-4cd2-94d4-14e5c9ad49fa" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesPricePerShare_9348c736-cad7-481f-9bfb-e9e3a9ee9c06" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesPricePerShare"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesPricePerShare_9348c736-cad7-481f-9bfb-e9e3a9ee9c06" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PrivatePlacementAgreementSaleOfSharesAmount_eb719f8d-a0da-4e59-9f8c-79a4868a51db" xlink:href="opk-20201231.xsd#opk_PrivatePlacementAgreementSaleOfSharesAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_PrivatePlacementAgreementSaleOfSharesAmount_eb719f8d-a0da-4e59-9f8c-79a4868a51db" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLinesOfCredit_c76c7c2d-7156-4255-b1bf-6af085be0550" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RepaymentsOfLinesOfCredit"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_RepaymentsOfLinesOfCredit_c76c7c2d-7156-4255-b1bf-6af085be0550" xlink:type="arc" order="14"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_bb521ae3-daa7-4f03-b9bf-8efb4d19cc8d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentFaceAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_bb521ae3-daa7-4f03-b9bf-8efb4d19cc8d" xlink:type="arc" order="15"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EquitySecurityFVNIOwnershipPercent_6b17581d-177f-427e-8246-8ede38fd0a36" xlink:href="opk-20201231.xsd#opk_EquitySecurityFVNIOwnershipPercent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_EquitySecurityFVNIOwnershipPercent_6b17581d-177f-427e-8246-8ede38fd0a36" xlink:type="arc" order="16"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DebtInstrumentConvertibleSharesIssued_1cacd68c-ecf6-48be-98b1-9a5617d36023" xlink:href="opk-20201231.xsd#opk_DebtInstrumentConvertibleSharesIssued"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_DebtInstrumentConvertibleSharesIssued_1cacd68c-ecf6-48be-98b1-9a5617d36023" xlink:type="arc" order="17"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EquityMethodInvestmentSharesPurchasedInPeriod_dcb2d2f6-af76-4663-8f47-b5276848bd79" xlink:href="opk-20201231.xsd#opk_EquityMethodInvestmentSharesPurchasedInPeriod"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_EquityMethodInvestmentSharesPurchasedInPeriod_dcb2d2f6-af76-4663-8f47-b5276848bd79" xlink:type="arc" order="18"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_e0325dd6-aa43-42f5-84d3-4f208ad19fe0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_e0325dd6-aa43-42f5-84d3-4f208ad19fe0" xlink:type="arc" order="19"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityNoteStockSplitConversionRatio1_b2f82db2-7412-4a58-811e-de2877dffa83" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquityNoteStockSplitConversionRatio1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_StockholdersEquityNoteStockSplitConversionRatio1_b2f82db2-7412-4a58-811e-de2877dffa83" xlink:type="arc" order="20"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ClassOfWarrantOrRightExerciseOfWarrantNumberOfSecuritiesReceived_ed1ffd78-72b5-4413-a200-9c25952136f2" xlink:href="opk-20201231.xsd#opk_ClassOfWarrantOrRightExerciseOfWarrantNumberOfSecuritiesReceived"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_ClassOfWarrantOrRightExerciseOfWarrantNumberOfSecuritiesReceived_ed1ffd78-72b5-4413-a200-9c25952136f2" xlink:type="arc" order="21"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromWarrantExercises_07e042b3-63ac-4559-b18e-c36fe10a4d1a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromWarrantExercises"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_ProceedsFromWarrantExercises_07e042b3-63ac-4559-b18e-c36fe10a4d1a" xlink:type="arc" order="22"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RelatedPartyTransactionFutureContributions_61b7730a-402d-4c3b-845a-8de6642f2874" xlink:href="opk-20201231.xsd#opk_RelatedPartyTransactionFutureContributions"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_RelatedPartyTransactionFutureContributions_61b7730a-402d-4c3b-845a-8de6642f2874" xlink:type="arc" order="23"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RelatedPartyTransactionFutureContributionsPeriod_b1765628-4052-44f7-92db-746be015d839" xlink:href="opk-20201231.xsd#opk_RelatedPartyTransactionFutureContributionsPeriod"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_RelatedPartyTransactionFutureContributionsPeriod_b1765628-4052-44f7-92db-746be015d839" xlink:type="arc" order="24"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AreaOfRealEstateProperty_4e2278da-141b-4477-91b5-c852c3efdfd6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AreaOfRealEstateProperty"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_AreaOfRealEstateProperty_4e2278da-141b-4477-91b5-c852c3efdfd6" xlink:type="arc" order="25"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OperatingLeasesMonthlyPaymentsYearOne_92794a13-31c8-4107-8774-678735f30790" xlink:href="opk-20201231.xsd#opk_OperatingLeasesMonthlyPaymentsYearOne"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_OperatingLeasesMonthlyPaymentsYearOne_92794a13-31c8-4107-8774-678735f30790" xlink:type="arc" order="26"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OperatingLeasesMonthlyPaymentsYearFive_762a40e1-ccca-42bd-aa02-f05f91cfb0d7" xlink:href="opk-20201231.xsd#opk_OperatingLeasesMonthlyPaymentsYearFive"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_opk_OperatingLeasesMonthlyPaymentsYearFive_762a40e1-ccca-42bd-aa02-f05f91cfb0d7" xlink:type="arc" order="27"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionExpensesFromTransactionsWithRelatedParty_9fe43c8c-6252-41b9-97b3-aff82356ad29" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionExpensesFromTransactionsWithRelatedParty"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_RelatedPartyTransactionExpensesFromTransactionsWithRelatedParty_9fe43c8c-6252-41b9-97b3-aff82356ad29" xlink:type="arc" order="28"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_ccc7352c-cb5d-47e1-9fa2-128dc1e41540" xlink:to="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_ad43fbb8-17c1-4c32-a997-f122d26b6474" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CounterpartyNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_srt_CounterpartyNameAxis_ad43fbb8-17c1-4c32-a997-f122d26b6474" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ad43fbb8-17c1-4c32-a997-f122d26b6474_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_ad43fbb8-17c1-4c32-a997-f122d26b6474" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ad43fbb8-17c1-4c32-a997-f122d26b6474_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_2d427b5a-834b-4fe0-8756-c5f080eed70e" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_ad43fbb8-17c1-4c32-a997-f122d26b6474" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_2d427b5a-834b-4fe0-8756-c5f080eed70e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MembersofSeniorManagementMember_8d298a21-921e-4cdc-8d9a-82c44c528973" xlink:href="opk-20201231.xsd#opk_MembersofSeniorManagementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_2d427b5a-834b-4fe0-8756-c5f080eed70e" xlink:to="loc_opk_MembersofSeniorManagementMember_8d298a21-921e-4cdc-8d9a-82c44c528973" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_42a62373-e48b-4204-9e7b-dda4b0f65ba6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_42a62373-e48b-4204-9e7b-dda4b0f65ba6" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_42a62373-e48b-4204-9e7b-dda4b0f65ba6_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_42a62373-e48b-4204-9e7b-dda4b0f65ba6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_42a62373-e48b-4204-9e7b-dda4b0f65ba6_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_cf344392-944d-4056-bec4-672e9978485f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_42a62373-e48b-4204-9e7b-dda4b0f65ba6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_cf344392-944d-4056-bec4-672e9978485f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IPOMember_a0621c4b-48c5-4620-87f4-a5164c9cf8b1" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IPOMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_cf344392-944d-4056-bec4-672e9978485f" xlink:to="loc_us-gaap_IPOMember_a0621c4b-48c5-4620-87f4-a5164c9cf8b1" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OverAllotmentOptionMember_0ddbfe81-c3e7-42db-ab29-a887940e9f8d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OverAllotmentOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_cf344392-944d-4056-bec4-672e9978485f" xlink:to="loc_us-gaap_OverAllotmentOptionMember_0ddbfe81-c3e7-42db-ab29-a887940e9f8d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_CreditFacilityAxis_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b" xlink:to="loc_us-gaap_CreditFacilityDomain_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_30c33213-7f5c-421d-b70d-f30a4b621128" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditFacilityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_c24e24a3-4aac-46f1-b350-a8b2e8b6d04b" xlink:to="loc_us-gaap_CreditFacilityDomain_30c33213-7f5c-421d-b70d-f30a4b621128" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_d356fd25-ae5d-4554-bbe0-882fb52ec922" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_30c33213-7f5c-421d-b70d-f30a4b621128" xlink:to="loc_us-gaap_LineOfCreditMember_d356fd25-ae5d-4554-bbe0-882fb52ec922" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevolvingCreditFacilityMember_db856b2f-2bc2-4cc3-8e38-77de6dd37150" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevolvingCreditFacilityMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_30c33213-7f5c-421d-b70d-f30a4b621128" xlink:to="loc_us-gaap_RevolvingCreditFacilityMember_db856b2f-2bc2-4cc3-8e38-77de6dd37150" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualAxis_8b5f9ab5-d552-4190-bef3-4de329bf08c6" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_srt_TitleOfIndividualAxis_8b5f9ab5-d552-4190-bef3-4de329bf08c6" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_8b5f9ab5-d552-4190-bef3-4de329bf08c6_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_TitleOfIndividualAxis_8b5f9ab5-d552-4190-bef3-4de329bf08c6" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_8b5f9ab5-d552-4190-bef3-4de329bf08c6_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_63e8506b-5166-4571-a5de-94443cd32a00" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_TitleOfIndividualWithRelationshipToEntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_TitleOfIndividualAxis_8b5f9ab5-d552-4190-bef3-4de329bf08c6" xlink:to="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_63e8506b-5166-4571-a5de-94443cd32a00" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChiefTechnicalOfficerMember_4f9d1e28-bfbc-4a67-82d0-9d25b3977d73" xlink:href="opk-20201231.xsd#opk_ChiefTechnicalOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_63e8506b-5166-4571-a5de-94443cd32a00" xlink:to="loc_opk_ChiefTechnicalOfficerMember_4f9d1e28-bfbc-4a67-82d0-9d25b3977d73" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ChiefExecutiveOfficerMember_16ffe5fb-d869-4571-bc56-2745de3c70e1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ChiefExecutiveOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_TitleOfIndividualWithRelationshipToEntityDomain_63e8506b-5166-4571-a5de-94443cd32a00" xlink:to="loc_srt_ChiefExecutiveOfficerMember_16ffe5fb-d869-4571-bc56-2745de3c70e1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_2737631d-d5c3-490b-b065-ecbb589ec159" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_2737631d-d5c3-490b-b065-ecbb589ec159" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_2737631d-d5c3-490b-b065-ecbb589ec159_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_2737631d-d5c3-490b-b065-ecbb589ec159" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_2737631d-d5c3-490b-b065-ecbb589ec159_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_e57869f6-2c47-4904-9147-4c0801c67e82" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_2737631d-d5c3-490b-b065-ecbb589ec159" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_e57869f6-2c47-4904-9147-4c0801c67e82" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_df47ab1d-5be7-41b4-8243-698980b88cfe" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LineOfCreditMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_e57869f6-2c47-4904-9147-4c0801c67e82" xlink:to="loc_us-gaap_LineOfCreditMember_df47ab1d-5be7-41b4-8243-698980b88cfe" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnsecuredDebtMember_7bb3012f-70da-4b27-a99f-0d6e7ee7a23d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_UnsecuredDebtMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_e57869f6-2c47-4904-9147-4c0801c67e82" xlink:to="loc_us-gaap_UnsecuredDebtMember_7bb3012f-70da-4b27-a99f-0d6e7ee7a23d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_615bb718-34cf-4b2e-9813-872b24db3d28" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleDebtMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_e57869f6-2c47-4904-9147-4c0801c67e82" xlink:to="loc_us-gaap_ConvertibleDebtMember_615bb718-34cf-4b2e-9813-872b24db3d28" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_d67384c9-f046-43c6-b5d8-1a1827264526" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_DebtInstrumentAxis_d67384c9-f046-43c6-b5d8-1a1827264526" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_d67384c9-f046-43c6-b5d8-1a1827264526_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_d67384c9-f046-43c6-b5d8-1a1827264526" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_d67384c9-f046-43c6-b5d8-1a1827264526_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_6d9c0e26-b651-408d-bc37-06a09486fb48" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_d67384c9-f046-43c6-b5d8-1a1827264526" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_6d9c0e26-b651-408d-bc37-06a09486fb48" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NewCreditAgreementMember_452c5f92-e77c-4ea8-9364-6f60e347ad9d" xlink:href="opk-20201231.xsd#opk_NewCreditAgreementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_6d9c0e26-b651-408d-bc37-06a09486fb48" xlink:to="loc_opk_NewCreditAgreementMember_452c5f92-e77c-4ea8-9364-6f60e347ad9d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_A5ConvertibleNotesMember_91299063-c524-41e2-8dd6-0315abb0528c" xlink:href="opk-20201231.xsd#opk_A5ConvertibleNotesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_6d9c0e26-b651-408d-bc37-06a09486fb48" xlink:to="loc_opk_A5ConvertibleNotesMember_91299063-c524-41e2-8dd6-0315abb0528c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_2efdc0ef-af47-4955-98e0-87bc9518805f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_2efdc0ef-af47-4955-98e0-87bc9518805f" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_2efdc0ef-af47-4955-98e0-87bc9518805f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2efdc0ef-af47-4955-98e0-87bc9518805f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_2efdc0ef-af47-4955-98e0-87bc9518805f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_0380ec70-6e13-460d-9805-9bfb3c408d3e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_2efdc0ef-af47-4955-98e0-87bc9518805f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_0380ec70-6e13-460d-9805-9bfb3c408d3e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SeriesAWarrantMember_fedcf9eb-3dc5-4c5c-8a90-121d9c03e751" xlink:href="opk-20201231.xsd#opk_SeriesAWarrantMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_0380ec70-6e13-460d-9805-9bfb3c408d3e" xlink:to="loc_opk_SeriesAWarrantMember_fedcf9eb-3dc5-4c5c-8a90-121d9c03e751" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SeriesBWarrantMember_f522f2c4-ee94-4242-8a05-0d2842b9b7c0" xlink:href="opk-20201231.xsd#opk_SeriesBWarrantMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_0380ec70-6e13-460d-9805-9bfb3c408d3e" xlink:to="loc_opk_SeriesBWarrantMember_f522f2c4-ee94-4242-8a05-0d2842b9b7c0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SeriesCWarrantMember_970b9091-101e-49f6-aba9-1a04fa4b007e" xlink:href="opk-20201231.xsd#opk_SeriesCWarrantMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_0380ec70-6e13-460d-9805-9bfb3c408d3e" xlink:to="loc_opk_SeriesCWarrantMember_970b9091-101e-49f6-aba9-1a04fa4b007e" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionAxis_99224a4f-b8ad-4339-84fa-3b3c75aa4dad" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_RelatedPartyTransactionAxis_99224a4f-b8ad-4339-84fa-3b3c75aa4dad" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionDomain_99224a4f-b8ad-4339-84fa-3b3c75aa4dad_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionAxis_99224a4f-b8ad-4339-84fa-3b3c75aa4dad" xlink:to="loc_us-gaap_RelatedPartyTransactionDomain_99224a4f-b8ad-4339-84fa-3b3c75aa4dad_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionAxis_99224a4f-b8ad-4339-84fa-3b3c75aa4dad" xlink:to="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_FederalTradeCommissionFilingFeesMember_a27eb59d-9fa9-4f4f-a1cf-82e12604ce16" xlink:href="opk-20201231.xsd#opk_FederalTradeCommissionFilingFeesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:to="loc_opk_FederalTradeCommissionFilingFeesMember_a27eb59d-9fa9-4f4f-a1cf-82e12604ce16" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OPKOTransactionSharesMember_82245152-10f7-447a-a560-88e4d642f6a0" xlink:href="opk-20201231.xsd#opk_OPKOTransactionSharesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:to="loc_opk_OPKOTransactionSharesMember_82245152-10f7-447a-a560-88e4d642f6a0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SharesReceivedUponClosingofXeneticTransactionMember_c688fb79-e3d4-47a9-b4e7-c3b273e92b4e" xlink:href="opk-20201231.xsd#opk_SharesReceivedUponClosingofXeneticTransactionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:to="loc_opk_SharesReceivedUponClosingofXeneticTransactionMember_c688fb79-e3d4-47a9-b4e7-c3b273e92b4e" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ReimbursementOfTravelExpenseMember_81f7ea9e-8276-439f-b7eb-bf979c2e0d9a" xlink:href="opk-20201231.xsd#opk_ReimbursementOfTravelExpenseMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionDomain_539df9de-f951-44b7-883a-8b47698cb2be" xlink:to="loc_opk_ReimbursementOfTravelExpenseMember_81f7ea9e-8276-439f-b7eb-bf979c2e0d9a" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61792046-e555-4ef5-9bda-f22c90920397" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61792046-e555-4ef5-9bda-f22c90920397" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_61792046-e555-4ef5-9bda-f22c90920397_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61792046-e555-4ef5-9bda-f22c90920397" xlink:to="loc_us-gaap_RelatedPartyDomain_61792046-e555-4ef5-9bda-f22c90920397_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RelatedPartyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_61792046-e555-4ef5-9bda-f22c90920397" xlink:to="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_AffiliatedEntityMember_42c97929-0955-4d27-9d20-d1af0c39cdb3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_AffiliatedEntityMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_srt_AffiliatedEntityMember_42c97929-0955-4d27-9d20-d1af0c39cdb3" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_DirectorMember_64c2853f-e5ec-4519-9ee9-64de2399f665" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_DirectorMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_srt_DirectorMember_64c2853f-e5ec-4519-9ee9-64de2399f665" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChiefTechnicalOfficerMember_48e8c3c3-a22a-42a4-ae89-33577bced397" xlink:href="opk-20201231.xsd#opk_ChiefTechnicalOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_opk_ChiefTechnicalOfficerMember_48e8c3c3-a22a-42a4-ae89-33577bced397" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ChiefExecutiveOfficerMember_c8eeccd1-c3ee-4e8d-a00f-935d6d933aec" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ChiefExecutiveOfficerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_srt_ChiefExecutiveOfficerMember_c8eeccd1-c3ee-4e8d-a00f-935d6d933aec" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DrFrostMember_b0a2e676-bb0f-4f30-9dc4-85ed3ca0b1c5" xlink:href="opk-20201231.xsd#opk_DrFrostMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_opk_DrFrostMember_b0a2e676-bb0f-4f30-9dc4-85ed3ca0b1c5" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioCardiaInc.Member_671dac96-d798-4bfc-90d1-dd25ea397994" xlink:href="opk-20201231.xsd#opk_BioCardiaInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_opk_BioCardiaInc.Member_671dac96-d798-4bfc-90d1-dd25ea397994" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DrFrostandMrPfennigerMember_30701d7b-1b17-4405-bc0c-f67775351676" xlink:href="opk-20201231.xsd#opk_DrFrostandMrPfennigerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_opk_DrFrostandMrPfennigerMember_30701d7b-1b17-4405-bc0c-f67775351676" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_FrostRealEstateHoldingsLLCMember_823b3020-217b-49fc-ae3a-8abcf70e472f" xlink:href="opk-20201231.xsd#opk_FrostRealEstateHoldingsLLCMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_1a478411-5534-4bdd-a87a-b285607b0f83" xlink:to="loc_opk_FrostRealEstateHoldingsLLCMember_823b3020-217b-49fc-ae3a-8abcf70e472f" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_83be340a-9e1d-453a-a7e3-3e75abefab90" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_83be340a-9e1d-453a-a7e3-3e75abefab90" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_83be340a-9e1d-453a-a7e3-3e75abefab90_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_83be340a-9e1d-453a-a7e3-3e75abefab90" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_83be340a-9e1d-453a-a7e3-3e75abefab90_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_83be340a-9e1d-453a-a7e3-3e75abefab90" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PharmsynthezMember_e1689674-787a-4cf4-876a-42606a4d421f" xlink:href="opk-20201231.xsd#opk_PharmsynthezMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_PharmsynthezMember_e1689674-787a-4cf4-876a-42606a4d421f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ZebraMember_827a5db3-187d-42a2-9c97-7c0b63ee3ef1" xlink:href="opk-20201231.xsd#opk_ZebraMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_ZebraMember_827a5db3-187d-42a2-9c97-7c0b63ee3ef1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NeovascMember_28a051cb-a154-4961-ab37-b9e7d0841951" xlink:href="opk-20201231.xsd#opk_NeovascMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_NeovascMember_28a051cb-a154-4961-ab37-b9e7d0841951" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChromadexCorporationMember_729d72b5-3ed9-4474-95e5-d325d6d949b6" xlink:href="opk-20201231.xsd#opk_ChromadexCorporationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_ChromadexCorporationMember_729d72b5-3ed9-4474-95e5-d325d6d949b6" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MabVaxTherapeuticsHoldingsInc.Member_26776a4f-4d7a-432a-98d5-3fbc8ae5bd95" xlink:href="opk-20201231.xsd#opk_MabVaxTherapeuticsHoldingsInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_MabVaxTherapeuticsHoldingsInc.Member_26776a4f-4d7a-432a-98d5-3fbc8ae5bd95" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CocrystalPharmaInc.Member_8c7fd815-041f-4dae-9aa6-d5236f2cbf3b" xlink:href="opk-20201231.xsd#opk_CocrystalPharmaInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_CocrystalPharmaInc.Member_8c7fd815-041f-4dae-9aa6-d5236f2cbf3b" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NIMSMember_80cfd466-f0cf-44e5-89b5-51775003f962" xlink:href="opk-20201231.xsd#opk_NIMSMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_NIMSMember_80cfd466-f0cf-44e5-89b5-51775003f962" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EloxxPharmaceuticalsMember_07210dfc-6574-447e-9b86-265bbf7c26f4" xlink:href="opk-20201231.xsd#opk_EloxxPharmaceuticalsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_EloxxPharmaceuticalsMember_07210dfc-6574-447e-9b86-265bbf7c26f4" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioCardiaInc.Member_045780b6-5898-409a-9829-2ae0e5fcb291" xlink:href="opk-20201231.xsd#opk_BioCardiaInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_BioCardiaInc.Member_045780b6-5898-409a-9829-2ae0e5fcb291" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CocrystalMember_685bd85a-edbd-4122-b2fe-6fa05723b8de" xlink:href="opk-20201231.xsd#opk_CocrystalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_CocrystalMember_685bd85a-edbd-4122-b2fe-6fa05723b8de" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_InCellDxIncMember_5870420e-64b6-42a6-8cfe-df1c08397ed7" xlink:href="opk-20201231.xsd#opk_InCellDxIncMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_InCellDxIncMember_5870420e-64b6-42a6-8cfe-df1c08397ed7" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DetectGenomixMember_8d4e001a-b870-4fc6-a482-81559a300596" xlink:href="opk-20201231.xsd#opk_DetectGenomixMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_13572d1e-13e2-4332-92b7-46479ab8b19c" xlink:to="loc_opk_DetectGenomixMember_8d4e001a-b870-4fc6-a482-81559a300596" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_daded113-79e2-4725-8c15-c0c20940424f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_us-gaap_StatementClassOfStockAxis_daded113-79e2-4725-8c15-c0c20940424f" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_daded113-79e2-4725-8c15-c0c20940424f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_daded113-79e2-4725-8c15-c0c20940424f" xlink:to="loc_us-gaap_ClassOfStockDomain_daded113-79e2-4725-8c15-c0c20940424f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_4a6425f0-855b-41d4-8d8a-2140d810a35a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ClassOfStockDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_daded113-79e2-4725-8c15-c0c20940424f" xlink:to="loc_us-gaap_ClassOfStockDomain_4a6425f0-855b-41d4-8d8a-2140d810a35a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_0d8d25ea-b153-4ed2-bd02-98cec95d3b1d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_4a6425f0-855b-41d4-8d8a-2140d810a35a" xlink:to="loc_us-gaap_CommonStockMember_0d8d25ea-b153-4ed2-bd02-98cec95d3b1d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_27332709-aedc-4668-a234-b1939680bf51" xlink:href="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.xsd#dei_LegalEntityAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_dei_LegalEntityAxis_27332709-aedc-4668-a234-b1939680bf51" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_27332709-aedc-4668-a234-b1939680bf51_default" xlink:href="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.xsd#dei_EntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_27332709-aedc-4668-a234-b1939680bf51" xlink:to="loc_dei_EntityDomain_27332709-aedc-4668-a234-b1939680bf51_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_33adb92b-a479-4901-b878-910b72d84647" xlink:href="https://xbrl.sec.gov/dei/2020/dei-2020-01-31.xsd#dei_EntityDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_27332709-aedc-4668-a234-b1939680bf51" xlink:to="loc_dei_EntityDomain_33adb92b-a479-4901-b878-910b72d84647" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MednaxServicesIncMember_6c44cb22-0f3a-4f41-aab1-d0fa9e69c49c" xlink:href="opk-20201231.xsd#opk_MednaxServicesIncMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_33adb92b-a479-4901-b878-910b72d84647" xlink:to="loc_opk_MednaxServicesIncMember_6c44cb22-0f3a-4f41-aab1-d0fa9e69c49c" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_XeneticBiosciencesInc.Member_83394355-4cef-4e14-83a9-28dd5f86ba5d" xlink:href="opk-20201231.xsd#opk_XeneticBiosciencesInc.Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_33adb92b-a479-4901-b878-910b72d84647" xlink:to="loc_opk_XeneticBiosciencesInc.Member_83394355-4cef-4e14-83a9-28dd5f86ba5d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MuseumofScienceIncMember_18c9ee84-e40c-442f-af4b-9ab81554d8b6" xlink:href="opk-20201231.xsd#opk_MuseumofScienceIncMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_33adb92b-a479-4901-b878-910b72d84647" xlink:to="loc_opk_MuseumofScienceIncMember_18c9ee84-e40c-442f-af4b-9ab81554d8b6" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesAxis_81fbca6a-3028-4267-811f-ddca81660e2f" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_a6c8d681-37fa-4dc5-a730-0e432862c107" xlink:to="loc_srt_ConsolidatedEntitiesAxis_81fbca6a-3028-4267-811f-ddca81660e2f" xlink:type="arc" order="13"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_81fbca6a-3028-4267-811f-ddca81660e2f_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidatedEntitiesAxis_81fbca6a-3028-4267-811f-ddca81660e2f" xlink:to="loc_srt_ConsolidatedEntitiesDomain_81fbca6a-3028-4267-811f-ddca81660e2f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_7564ce95-3f4d-47bd-9f3a-2ca1d9848792" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidatedEntitiesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidatedEntitiesAxis_81fbca6a-3028-4267-811f-ddca81660e2f" xlink:to="loc_srt_ConsolidatedEntitiesDomain_7564ce95-3f4d-47bd-9f3a-2ca1d9848792" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_7c08fc34-8e5f-4cdd-9272-d47ba644e2bd" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidatedEntitiesDomain_7564ce95-3f4d-47bd-9f3a-2ca1d9848792" xlink:to="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_7c08fc34-8e5f-4cdd-9272-d47ba644e2bd" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/EmployeeBenefitPlans" xlink:type="simple" xlink:href="opk-20201231.xsd#EmployeeBenefitPlans"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EmployeeBenefitPlans" xlink:type="extended" id="i31b108734b3f4607b8e4296ac2ce8c4d_EmployeeBenefitPlans"/>
<link:roleRef roleURI="http://www.opko.com/role/EmployeeBenefitPlansNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#EmployeeBenefitPlansNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/EmployeeBenefitPlansNarrativeDetails" xlink:type="extended" id="i12517050239b426dbc636e4d3eb77e38_EmployeeBenefitPlansNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanDisclosureLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeePercent_16be8356-f13a-4d7b-9714-7072b0988d97" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeePercent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:to="loc_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeePercent_16be8356-f13a-4d7b-9714-7072b0988d97" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch_89829d80-c092-4e70-b860-08fb6d44c811" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:to="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch_89829d80-c092-4e70-b860-08fb6d44c811" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent_860a9a85-0763-4632-992b-f07172383dba" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:to="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent_860a9a85-0763-4632-992b-f07172383dba" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount_50a51721-6afc-42e0-8647-603146a6aa8b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:to="loc_us-gaap_DefinedContributionPlanEmployerDiscretionaryContributionAmount_50a51721-6afc-42e0-8647-603146a6aa8b" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanTable_26f8745d-297e-402e-b2b3-497e0798af2f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DefinedContributionPlanTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DefinedContributionPlanDisclosureLineItems_47362e4c-e99c-4fe8-a233-0fe851de862d" xlink:to="loc_us-gaap_DefinedContributionPlanTable_26f8745d-297e-402e-b2b3-497e0798af2f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanNameAxis_73229b73-79f9-407f-959a-c0ec1717cf07" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetirementPlanNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DefinedContributionPlanTable_26f8745d-297e-402e-b2b3-497e0798af2f" xlink:to="loc_us-gaap_RetirementPlanNameAxis_73229b73-79f9-407f-959a-c0ec1717cf07" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanNameDomain_73229b73-79f9-407f-959a-c0ec1717cf07_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetirementPlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RetirementPlanNameAxis_73229b73-79f9-407f-959a-c0ec1717cf07" xlink:to="loc_us-gaap_RetirementPlanNameDomain_73229b73-79f9-407f-959a-c0ec1717cf07_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanNameDomain_58dff271-00f2-4d89-a1c8-a5e42e70e5f9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetirementPlanNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RetirementPlanNameAxis_73229b73-79f9-407f-959a-c0ec1717cf07" xlink:to="loc_us-gaap_RetirementPlanNameDomain_58dff271-00f2-4d89-a1c8-a5e42e70e5f9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OPKOHealthSavingsandRetirementPlanMember_0f269b49-d342-42ea-a25e-7e7c60a74b4e" xlink:href="opk-20201231.xsd#opk_OPKOHealthSavingsandRetirementPlanMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RetirementPlanNameDomain_58dff271-00f2-4d89-a1c8-a5e42e70e5f9" xlink:to="loc_opk_OPKOHealthSavingsandRetirementPlanMember_0f269b49-d342-42ea-a25e-7e7c60a74b4e" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/CommitmentsandContingencies" xlink:type="simple" xlink:href="opk-20201231.xsd#CommitmentsandContingencies"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CommitmentsandContingencies" xlink:type="extended" id="ib718253eba814a828ebfece6aeb8213b_CommitmentsandContingencies"/>
<link:roleRef roleURI="http://www.opko.com/role/CommitmentsandContingenciesNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#CommitmentsandContingenciesNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/CommitmentsandContingenciesNarrativeDetails" xlink:type="extended" id="i28a547ab22f842a18c7fbf924ea5f0f6_CommitmentsandContingenciesNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionContingentConsiderationLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_8116b676-b4a6-46c6-8963-dd998ae539d6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_8116b676-b4a6-46c6-8963-dd998ae539d6" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_NumberOfClassActionLawsuits_e4815d3c-4238-4ee2-be05-dab2f85be853" xlink:href="opk-20201231.xsd#opk_NumberOfClassActionLawsuits"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_opk_NumberOfClassActionLawsuits_e4815d3c-4238-4ee2-be05-dab2f85be853" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForLegalSettlements_ee6c79ad-43df-4f27-b120-3dc599c24224" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsForLegalSettlements"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_PaymentsForLegalSettlements_ee6c79ad-43df-4f27-b120-3dc599c24224" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationSettlementAmountAwardedToOtherParty_168576a2-a1cf-4386-952c-4772800b4bf9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LitigationSettlementAmountAwardedToOtherParty"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_LitigationSettlementAmountAwardedToOtherParty_168576a2-a1cf-4386-952c-4772800b4bf9" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PaymentsForOverpaymentFinding_9f515b8b-b6da-45d8-b767-993ded3467bd" xlink:href="opk-20201231.xsd#opk_PaymentsForOverpaymentFinding"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_opk_PaymentsForOverpaymentFinding_9f515b8b-b6da-45d8-b767-993ded3467bd" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_1ef5ed68-ce02-418f-ba24-1aef4915e182" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SeveranceCosts1"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_SeveranceCosts1_1ef5ed68-ce02-418f-ba24-1aef4915e182" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PurchaseObligation_a59c75bd-d807-4536-9253-bf2462e65db9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PurchaseObligation"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_PurchaseObligation_a59c75bd-d807-4536-9253-bf2462e65db9" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionContingentConsiderationLineItems_0a458a2d-b8f1-4d23-8ba4-4547a3ebe33f" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_851ac4f3-3460-4eda-9a41-ee71dea99413" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_851ac4f3-3460-4eda-9a41-ee71dea99413" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_851ac4f3-3460-4eda-9a41-ee71dea99413_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_851ac4f3-3460-4eda-9a41-ee71dea99413" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_851ac4f3-3460-4eda-9a41-ee71dea99413_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_70529f66-a23d-4ca2-a480-736955231233" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_851ac4f3-3460-4eda-9a41-ee71dea99413" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_70529f66-a23d-4ca2-a480-736955231233" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioReferenceMember_ca14f4fa-bb4c-4538-bafc-699d74d021e2" xlink:href="opk-20201231.xsd#opk_BioReferenceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_70529f66-a23d-4ca2-a480-736955231233" xlink:to="loc_opk_BioReferenceMember_ca14f4fa-bb4c-4538-bafc-699d74d021e2" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_236245b9-0cf4-4f39-bbbe-6fec44a86937" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_236245b9-0cf4-4f39-bbbe-6fec44a86937" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_236245b9-0cf4-4f39-bbbe-6fec44a86937_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_236245b9-0cf4-4f39-bbbe-6fec44a86937" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_236245b9-0cf4-4f39-bbbe-6fec44a86937_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_b5c2f9c4-50c5-4cba-ad14-c94f4784dfff" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_236245b9-0cf4-4f39-bbbe-6fec44a86937" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_b5c2f9c4-50c5-4cba-ad14-c94f4784dfff" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesMember_74ba6257-bbd0-41b6-9a8f-0f3f1d652f40" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_b5c2f9c4-50c5-4cba-ad14-c94f4784dfff" xlink:to="loc_us-gaap_AccruedLiabilitiesMember_74ba6257-bbd0-41b6-9a8f-0f3f1d652f40" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNoncurrentLiabilitiesMember_2beb96dd-6020-4a53-a31e-93da9958e83f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNoncurrentLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_b5c2f9c4-50c5-4cba-ad14-c94f4784dfff" xlink:to="loc_us-gaap_OtherNoncurrentLiabilitiesMember_2beb96dd-6020-4a53-a31e-93da9958e83f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusAxis_da4af86a-6e81-4ad0-bbaa-c2066915747a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LitigationStatusAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:to="loc_us-gaap_LitigationStatusAxis_da4af86a-6e81-4ad0-bbaa-c2066915747a" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusDomain_da4af86a-6e81-4ad0-bbaa-c2066915747a_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LitigationStatusDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LitigationStatusAxis_da4af86a-6e81-4ad0-bbaa-c2066915747a" xlink:to="loc_us-gaap_LitigationStatusDomain_da4af86a-6e81-4ad0-bbaa-c2066915747a_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusDomain_3758edc7-bb0c-44c1-b216-5163e0415c24" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LitigationStatusDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LitigationStatusAxis_da4af86a-6e81-4ad0-bbaa-c2066915747a" xlink:to="loc_us-gaap_LitigationStatusDomain_3758edc7-bb0c-44c1-b216-5163e0415c24" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SettledLitigationMember_ae0c1895-8c71-4849-afff-4c2e54cfe2dc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SettledLitigationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LitigationStatusDomain_3758edc7-bb0c-44c1-b216-5163e0415c24" xlink:to="loc_us-gaap_SettledLitigationMember_ae0c1895-8c71-4849-afff-4c2e54cfe2dc" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PendingLitigationMember_5dd49882-5c1e-47ce-b225-e1d84d4b35b6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PendingLitigationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LitigationStatusDomain_3758edc7-bb0c-44c1-b216-5163e0415c24" xlink:to="loc_us-gaap_PendingLitigationMember_5dd49882-5c1e-47ce-b225-e1d84d4b35b6" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_2ba1770a-d497-4626-99d5-ebfb493e842f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionContingentConsiderationTable_11d121dc-b014-4ba9-8d1f-13c48bdda753" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_2ba1770a-d497-4626-99d5-ebfb493e842f" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_2ba1770a-d497-4626-99d5-ebfb493e842f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_2ba1770a-d497-4626-99d5-ebfb493e842f" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_2ba1770a-d497-4626-99d5-ebfb493e842f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_12d90e8f-b679-4cbf-af33-5bdeefae7343" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_2ba1770a-d497-4626-99d5-ebfb493e842f" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_12d90e8f-b679-4cbf-af33-5bdeefae7343" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_b220986a-43b8-4460-8e9d-9449b8da7df6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SubsequentEventMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_12d90e8f-b679-4cbf-af33-5bdeefae7343" xlink:to="loc_us-gaap_SubsequentEventMember_b220986a-43b8-4460-8e9d-9449b8da7df6" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognition" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognition"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognition" xlink:type="extended" id="ia76ce0d83f6b40dea8d77739288d793f_RevenueRecognition"/>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognitionTables" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognitionTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognitionTables" xlink:type="extended" id="ibd76b8dce4034de5888548daed0cbd51_RevenueRecognitionTables"/>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognitionNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognitionNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognitionNarrativeDetails" xlink:type="extended" id="ia1599feade1441a1a34a522b6b4a909f_RevenueRecognitionNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerPerformanceObligationSatisfiedInPreviousPeriod_6a34bb13-3606-4126-84c4-8b6abc352452" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerPerformanceObligationSatisfiedInPreviousPeriod"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_us-gaap_ContractWithCustomerPerformanceObligationSatisfiedInPreviousPeriod_6a34bb13-3606-4126-84c4-8b6abc352452" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AccruedExpensePayorOverpaymentReimbursementLiability_06b9730f-b8de-428e-929e-cf1a6bd1e7e0" xlink:href="opk-20201231.xsd#opk_AccruedExpensePayorOverpaymentReimbursementLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_opk_AccruedExpensePayorOverpaymentReimbursementLiability_06b9730f-b8de-428e-929e-cf1a6bd1e7e0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_5eb8d52e-164b-41c5-a3c2-dba7b9189808" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_5eb8d52e-164b-41c5-a3c2-dba7b9189808" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7d6ed6df-e453-496d-a990-1470f03edd10" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_7d6ed6df-e453-496d-a990-1470f03edd10" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_40b0f255-5841-47c0-9305-6c227405ba65" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_us-gaap_ContractWithCustomerLiability_40b0f255-5841-47c0-9305-6c227405ba65" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_7e27237e-6d93-4794-b100-8b1cb5611074" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_66f039c0-6577-424d-9a51-cfad15fe69af" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_7e27237e-6d93-4794-b100-8b1cb5611074" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_b53a13d9-720e-462a-a699-18d14a13216f" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CounterpartyNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_7e27237e-6d93-4794-b100-8b1cb5611074" xlink:to="loc_srt_CounterpartyNameAxis_b53a13d9-720e-462a-a699-18d14a13216f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b53a13d9-720e-462a-a699-18d14a13216f_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_b53a13d9-720e-462a-a699-18d14a13216f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b53a13d9-720e-462a-a699-18d14a13216f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dfea7e4-d8c2-4d69-86a1-76eeec59ca9d" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_b53a13d9-720e-462a-a699-18d14a13216f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dfea7e4-d8c2-4d69-86a1-76eeec59ca9d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PfizerMember_06b20953-9698-4606-a4f3-4c314c03179e" xlink:href="opk-20201231.xsd#opk_PfizerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dfea7e4-d8c2-4d69-86a1-76eeec59ca9d" xlink:to="loc_opk_PfizerMember_06b20953-9698-4606-a4f3-4c314c03179e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ViforFreseniusMedicalCarePharmaLtdMember_9b4afd82-d047-4f6e-ba6d-eb19fef6bbcb" xlink:href="opk-20201231.xsd#opk_ViforFreseniusMedicalCarePharmaLtdMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dfea7e4-d8c2-4d69-86a1-76eeec59ca9d" xlink:to="loc_opk_ViforFreseniusMedicalCarePharmaLtdMember_9b4afd82-d047-4f6e-ba6d-eb19fef6bbcb" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_BioReferenceMember_c2cf9133-a065-4e6e-996e-2919b24cc953" xlink:href="opk-20201231.xsd#opk_BioReferenceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0dfea7e4-d8c2-4d69-86a1-76eeec59ca9d" xlink:to="loc_opk_BioReferenceMember_c2cf9133-a065-4e6e-996e-2919b24cc953" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_5540499c-1371-4c8f-b5fa-4cd352462d04" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_7e27237e-6d93-4794-b100-8b1cb5611074" xlink:to="loc_srt_ProductOrServiceAxis_5540499c-1371-4c8f-b5fa-4cd352462d04" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_5540499c-1371-4c8f-b5fa-4cd352462d04_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_5540499c-1371-4c8f-b5fa-4cd352462d04" xlink:to="loc_srt_ProductsAndServicesDomain_5540499c-1371-4c8f-b5fa-4cd352462d04_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_17c7dee2-ff4b-4e2e-b9fa-066c3689217d" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_5540499c-1371-4c8f-b5fa-4cd352462d04" xlink:to="loc_srt_ProductsAndServicesDomain_17c7dee2-ff4b-4e2e-b9fa-066c3689217d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RayaldeeMember_69e826d1-c20c-42fe-84dd-9ec764e4367e" xlink:href="opk-20201231.xsd#opk_RayaldeeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_17c7dee2-ff4b-4e2e-b9fa-066c3689217d" xlink:to="loc_opk_RayaldeeMember_69e826d1-c20c-42fe-84dd-9ec764e4367e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TransferOfIntellectualPropertyAndOtherMember_8eb79d88-9adb-4344-902b-fea925a3117a" xlink:href="opk-20201231.xsd#opk_TransferOfIntellectualPropertyAndOtherMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_17c7dee2-ff4b-4e2e-b9fa-066c3689217d" xlink:to="loc_opk_TransferOfIntellectualPropertyAndOtherMember_8eb79d88-9adb-4344-902b-fea925a3117a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_90950a15-834a-4a99-890b-2cda49cdff5d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TypeOfArrangementAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_7e27237e-6d93-4794-b100-8b1cb5611074" xlink:to="loc_us-gaap_TypeOfArrangementAxis_90950a15-834a-4a99-890b-2cda49cdff5d" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_90950a15-834a-4a99-890b-2cda49cdff5d_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_90950a15-834a-4a99-890b-2cda49cdff5d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_90950a15-834a-4a99-890b-2cda49cdff5d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ab296fd4-127f-4886-b726-ed81d9f5014c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_90950a15-834a-4a99-890b-2cda49cdff5d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ab296fd4-127f-4886-b726-ed81d9f5014c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_f63541b6-272b-4fec-8820-f64ce7af5ca5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_ab296fd4-127f-4886-b726-ed81d9f5014c" xlink:to="loc_us-gaap_ProductMember_f63541b6-272b-4fec-8820-f64ce7af5ca5" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognitionScheduleofDisaggregationofRevenueDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognitionScheduleofDisaggregationofRevenueDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognitionScheduleofDisaggregationofRevenueDetails" xlink:type="extended" id="i689762dd3c9b4838a4a4d1fad912ea10_RevenueRecognitionScheduleofDisaggregationofRevenueDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_070c6812-6327-46a1-9441-d9d32ebe692e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_df9c3cc0-2fcc-4224-a76c-8e949b188e3b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_070c6812-6327-46a1-9441-d9d32ebe692e" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_df9c3cc0-2fcc-4224-a76c-8e949b188e3b" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_d8a4f993-08ff-4801-b34c-ff003a0f7601" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_070c6812-6327-46a1-9441-d9d32ebe692e" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_d8a4f993-08ff-4801-b34c-ff003a0f7601" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_d8a4f993-08ff-4801-b34c-ff003a0f7601" xlink:to="loc_srt_ProductOrServiceAxis_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7" xlink:to="loc_srt_ProductsAndServicesDomain_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_b2ad3e81-8b1b-4f7e-8da2-b7599ab785e7" xlink:to="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_HealthInsurersMember_be4cdebb-f367-470a-9f3f-3bed1adad680" xlink:href="opk-20201231.xsd#opk_HealthInsurersMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:to="loc_opk_HealthInsurersMember_be4cdebb-f367-470a-9f3f-3bed1adad680" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_GovernmentPayersMember_f083b0d5-64e6-4c24-809a-7bd42d766dcd" xlink:href="opk-20201231.xsd#opk_GovernmentPayersMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:to="loc_opk_GovernmentPayersMember_f083b0d5-64e6-4c24-809a-7bd42d766dcd" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ClientPayersMember_b27b8a15-7a10-4002-a9dd-29875df3317f" xlink:href="opk-20201231.xsd#opk_ClientPayersMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:to="loc_opk_ClientPayersMember_b27b8a15-7a10-4002-a9dd-29875df3317f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PatientsMember_4f52510a-d078-41ef-87a0-852b3ce27d30" xlink:href="opk-20201231.xsd#opk_PatientsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:to="loc_opk_PatientsMember_4f52510a-d078-41ef-87a0-852b3ce27d30" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_a0159328-b22a-4f5c-952d-95435dd3d76c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ServiceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_b2505776-466c-45ba-bfa4-99ccb4b84efd" xlink:to="loc_us-gaap_ServiceMember_a0159328-b22a-4f5c-952d-95435dd3d76c" xlink:type="arc" order="4"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognitionScheduleofProductSalesAllowancesandAccrualsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognitionScheduleofProductSalesAllowancesandAccrualsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognitionScheduleofProductSalesAllowancesandAccrualsDetails" xlink:type="extended" id="ia13de23d5d604b92b76fd9b7957922ee_RevenueRecognitionScheduleofProductSalesAllowancesandAccrualsDetails">
<link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_f4b48a01-b978-48a8-8c4d-7eb37c8dfdd6" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward_a72c7cb5-22e7-485d-9297-1eee3d4f7567" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_f4b48a01-b978-48a8-8c4d-7eb37c8dfdd6" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward_a72c7cb5-22e7-485d-9297-1eee3d4f7567" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivable_8fdfb95e-fedb-4286-8214-6dac6e660853" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward_a72c7cb5-22e7-485d-9297-1eee3d4f7567" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivable_8fdfb95e-fedb-4286-8214-6dac6e660853" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProvisionForDoubtfulAccounts_89056f3f-baf0-4a86-b2aa-cae09771ee74" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProvisionForDoubtfulAccounts"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward_a72c7cb5-22e7-485d-9297-1eee3d4f7567" xlink:to="loc_us-gaap_ProvisionForDoubtfulAccounts_89056f3f-baf0-4a86-b2aa-cae09771ee74" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AllowanceForDoubtfulAccountsReceivableDecreaseCreditsOrPayments_4e146039-c0a3-46e1-9167-01a765c765b7" xlink:href="opk-20201231.xsd#opk_AllowanceForDoubtfulAccountsReceivableDecreaseCreditsOrPayments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableRollforward_a72c7cb5-22e7-485d-9297-1eee3d4f7567" xlink:to="loc_opk_AllowanceForDoubtfulAccountsReceivableDecreaseCreditsOrPayments_4e146039-c0a3-46e1-9167-01a765c765b7" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivable_800e0a39-cae0-489e-8794-7bc1a9c270cf" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivable"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_e351a3ce-3c09-4cd5-95c4-b73f57fb6f24" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_f4b48a01-b978-48a8-8c4d-7eb37c8dfdd6" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_e351a3ce-3c09-4cd5-95c4-b73f57fb6f24" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_AllowanceForDoubtfulAccountsProvisionForAllowanceAsPercentOfGrossSales_69fd248b-11a9-4576-9001-70ccaac32092" xlink:href="opk-20201231.xsd#opk_AllowanceForDoubtfulAccountsProvisionForAllowanceAsPercentOfGrossSales"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_f4b48a01-b978-48a8-8c4d-7eb37c8dfdd6" xlink:to="loc_opk_AllowanceForDoubtfulAccountsProvisionForAllowanceAsPercentOfGrossSales_69fd248b-11a9-4576-9001-70ccaac32092" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_0d108da4-294b-4a8e-a245-40077182870f" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_f4b48a01-b978-48a8-8c4d-7eb37c8dfdd6" xlink:to="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_0d108da4-294b-4a8e-a245-40077182870f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_0d108da4-294b-4a8e-a245-40077182870f" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_b1365aac-f92b-4372-8da5-c5effbc44677" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_dd3c196a-b24f-4960-b2ad-00ebbc0d01c7" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_b1365aac-f92b-4372-8da5-c5effbc44677" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ChargebacksDiscountsRebatesAndFeesMember_f657a0d8-1841-4142-a906-a37f5cfa5782" xlink:href="opk-20201231.xsd#opk_ChargebacksDiscountsRebatesAndFeesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_b1365aac-f92b-4372-8da5-c5effbc44677" xlink:to="loc_opk_ChargebacksDiscountsRebatesAndFeesMember_f657a0d8-1841-4142-a906-a37f5cfa5782" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_GovernmentalMember_b9e513cc-a959-4d16-854f-feed73edb4d0" xlink:href="opk-20201231.xsd#opk_GovernmentalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_b1365aac-f92b-4372-8da5-c5effbc44677" xlink:to="loc_opk_GovernmentalMember_b9e513cc-a959-4d16-854f-feed73edb4d0" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SalesReturnsMember_e1de7e6d-3a4d-40ee-8bc8-b680f89872fc" xlink:href="opk-20201231.xsd#opk_SalesReturnsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_b1365aac-f92b-4372-8da5-c5effbc44677" xlink:to="loc_opk_SalesReturnsMember_e1de7e6d-3a4d-40ee-8bc8-b680f89872fc" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_84659855-8e7c-46c8-8db2-2926fe491f5f" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_0d108da4-294b-4a8e-a245-40077182870f" xlink:to="loc_srt_ProductOrServiceAxis_84659855-8e7c-46c8-8db2-2926fe491f5f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_84659855-8e7c-46c8-8db2-2926fe491f5f_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_84659855-8e7c-46c8-8db2-2926fe491f5f" xlink:to="loc_srt_ProductsAndServicesDomain_84659855-8e7c-46c8-8db2-2926fe491f5f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_56c7000e-aa4a-4f26-953c-594351830ea1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_84659855-8e7c-46c8-8db2-2926fe491f5f" xlink:to="loc_srt_ProductsAndServicesDomain_56c7000e-aa4a-4f26-953c-594351830ea1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RayaldeeMember_aa35e2e7-7dc0-4594-9479-afc5c72e093c" xlink:href="opk-20201231.xsd#opk_RayaldeeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_56c7000e-aa4a-4f26-953c-594351830ea1" xlink:to="loc_opk_RayaldeeMember_aa35e2e7-7dc0-4594-9479-afc5c72e093c" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/RevenueRecognitionChangesinContractualLiabilitiesBalanceDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#RevenueRecognitionChangesinContractualLiabilitiesBalanceDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/RevenueRecognitionChangesinContractualLiabilitiesBalanceDetails" xlink:type="extended" id="i5ea1ec4e7ed94428915bdec19f377b58_RevenueRecognitionChangesinContractualLiabilitiesBalanceDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/StrategicAlliances" xlink:type="simple" xlink:href="opk-20201231.xsd#StrategicAlliances"/>
<link:definitionLink xlink:role="http://www.opko.com/role/StrategicAlliances" xlink:type="extended" id="i32b87f88226346c88226008b55426b22_StrategicAlliances"/>
<link:roleRef roleURI="http://www.opko.com/role/StrategicAlliancesNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#StrategicAlliancesNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/StrategicAlliancesNarrativeDetails" xlink:type="extended" id="iea96765e12ec4722a5301421d7481da8_StrategicAlliancesNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ProceedsFromDevelopmentAndLicenseAgreementUpfrontPayment_0aeac897-ceb8-42cf-9179-380359f840c5" xlink:href="opk-20201231.xsd#opk_ProceedsFromDevelopmentAndLicenseAgreementUpfrontPayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_ProceedsFromDevelopmentAndLicenseAgreementUpfrontPayment_0aeac897-ceb8-42cf-9179-380359f840c5" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ProceedsFromDevelopmentAndLicenseAgreementMilestonePayment_9a3b04e2-981e-4188-9d7a-2aeb0f0f9f9e" xlink:href="opk-20201231.xsd#opk_ProceedsFromDevelopmentAndLicenseAgreementMilestonePayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_ProceedsFromDevelopmentAndLicenseAgreementMilestonePayment_9a3b04e2-981e-4188-9d7a-2aeb0f0f9f9e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_b36093df-da6f-4b16-b618-b5b043a9a954" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_b36093df-da6f-4b16-b618-b5b043a9a954" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_fbb6ca7c-dd6b-40fc-a489-cb062ec7ca63" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_fbb6ca7c-dd6b-40fc-a489-cb062ec7ca63" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeArrangementMaximumMilestonePayments_3e0f8c4c-84b8-4e86-90fb-6440cdbbf600" xlink:href="opk-20201231.xsd#opk_CollaborativeArrangementMaximumMilestonePayments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeArrangementMaximumMilestonePayments_3e0f8c4c-84b8-4e86-90fb-6440cdbbf600" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromLicenseFeesReceived_e4355b69-a749-4cdd-804d-08ea7a648580" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromLicenseFeesReceived"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_ProceedsFromLicenseFeesReceived_e4355b69-a749-4cdd-804d-08ea7a648580" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeAgreementAdditionalMilestonePayment_024c7ff5-444b-4704-9679-d9bed1524d98" xlink:href="opk-20201231.xsd#opk_CollaborativeAgreementAdditionalMilestonePayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeAgreementAdditionalMilestonePayment_024c7ff5-444b-4704-9679-d9bed1524d98" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeArrangement.MaximumMilestonePayments_df8908f8-bf56-41e9-bb88-7ee30dbcffdb" xlink:href="opk-20201231.xsd#opk_CollaborativeArrangement.MaximumMilestonePayments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeArrangement.MaximumMilestonePayments_df8908f8-bf56-41e9-bb88-7ee30dbcffdb" xlink:type="arc" order="7"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeArrangementAnnualHeightVelocityatPointinTime_d3e921c3-a185-4e98-b99c-5a040c69fe20" xlink:href="opk-20201231.xsd#opk_CollaborativeArrangementAnnualHeightVelocityatPointinTime"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeArrangementAnnualHeightVelocityatPointinTime_d3e921c3-a185-4e98-b99c-5a040c69fe20" xlink:type="arc" order="8"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeArrangementUpfrontPayment_fc922836-b598-47a4-ab2a-2d1cb5fea736" xlink:href="opk-20201231.xsd#opk_CollaborativeArrangementUpfrontPayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeArrangementUpfrontPayment_fc922836-b598-47a4-ab2a-2d1cb5fea736" xlink:type="arc" order="9"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_8f5d1e85-6f5e-4dd4-932b-38a4164af964" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ContractWithCustomerLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_ContractWithCustomerLiability_8f5d1e85-6f5e-4dd4-932b-38a4164af964" xlink:type="arc" order="10"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_CollaborativeArrangementMilestonePayment_25019858-31b5-41d5-91c9-f74205ed1f90" xlink:href="opk-20201231.xsd#opk_CollaborativeArrangementMilestonePayment"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_opk_CollaborativeArrangementMilestonePayment_25019858-31b5-41d5-91c9-f74205ed1f90" xlink:type="arc" order="11"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_8c0c77dd-ee7f-4284-ab72-e360a35e4232" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_8c0c77dd-ee7f-4284-ab72-e360a35e4232" xlink:type="arc" order="12"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c241f3fe-530f-4f6b-bb57-3872775563f9" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_e0492e3b-3d3c-492b-892a-7044bf925315" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TypeOfArrangementAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_us-gaap_TypeOfArrangementAxis_e0492e3b-3d3c-492b-892a-7044bf925315" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_e0492e3b-3d3c-492b-892a-7044bf925315_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_e0492e3b-3d3c-492b-892a-7044bf925315" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_e0492e3b-3d3c-492b-892a-7044bf925315_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_aae8983d-7be5-412f-8fad-028b2094c2c9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_e0492e3b-3d3c-492b-892a-7044bf925315" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_aae8983d-7be5-412f-8fad-028b2094c2c9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_ff1ffe28-3117-403d-8adf-7a8dacfd0843" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_aae8983d-7be5-412f-8fad-028b2094c2c9" xlink:to="loc_us-gaap_ProductMember_ff1ffe28-3117-403d-8adf-7a8dacfd0843" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MilestoneAxis_6ad27a99-f3a4-4214-8a11-4f52b61badcb" xlink:href="opk-20201231.xsd#opk_MilestoneAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_opk_MilestoneAxis_6ad27a99-f3a4-4214-8a11-4f52b61badcb" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MilestoneDomain_6ad27a99-f3a4-4214-8a11-4f52b61badcb_default" xlink:href="opk-20201231.xsd#opk_MilestoneDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_opk_MilestoneAxis_6ad27a99-f3a4-4214-8a11-4f52b61badcb" xlink:to="loc_opk_MilestoneDomain_6ad27a99-f3a4-4214-8a11-4f52b61badcb_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_MilestoneDomain_2d363561-0404-4593-ac31-81931976797a" xlink:href="opk-20201231.xsd#opk_MilestoneDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_opk_MilestoneAxis_6ad27a99-f3a4-4214-8a11-4f52b61badcb" xlink:to="loc_opk_MilestoneDomain_2d363561-0404-4593-ac31-81931976797a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PhaseTwoInitiationMember_ae6b41ba-0e2d-461d-9718-7818fbccd245" xlink:href="opk-20201231.xsd#opk_PhaseTwoInitiationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_MilestoneDomain_2d363561-0404-4593-ac31-81931976797a" xlink:to="loc_opk_PhaseTwoInitiationMember_ae6b41ba-0e2d-461d-9718-7818fbccd245" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RegulatoryAndDevelopmentMember_88716734-02f0-46f7-93bf-9def18712c91" xlink:href="opk-20201231.xsd#opk_RegulatoryAndDevelopmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_MilestoneDomain_2d363561-0404-4593-ac31-81931976797a" xlink:to="loc_opk_RegulatoryAndDevelopmentMember_88716734-02f0-46f7-93bf-9def18712c91" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SalesRevenueMember_9952844f-2910-4b07-849e-82f34a1faa77" xlink:href="opk-20201231.xsd#opk_SalesRevenueMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_MilestoneDomain_2d363561-0404-4593-ac31-81931976797a" xlink:to="loc_opk_SalesRevenueMember_9952844f-2910-4b07-849e-82f34a1faa77" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_srt_RangeAxis_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad" xlink:to="loc_srt_RangeMember_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9a9b0668-9322-4b7d-9d5d-ce660715b116" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_ad8d0475-06d9-40e8-8075-4aa6d09fe4ad" xlink:to="loc_srt_RangeMember_9a9b0668-9322-4b7d-9d5d-ce660715b116" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_06b7236f-61d1-4d93-abd0-36062120eb93" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MinimumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_9a9b0668-9322-4b7d-9d5d-ce660715b116" xlink:to="loc_srt_MinimumMember_06b7236f-61d1-4d93-abd0-36062120eb93" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_788a10d5-2f5f-4291-9a53-71f73ed5c8e4" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_MaximumMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_9a9b0668-9322-4b7d-9d5d-ce660715b116" xlink:to="loc_srt_MaximumMember_788a10d5-2f5f-4291-9a53-71f73ed5c8e4" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_a66aa47f-7269-4d29-a295-2d3718b9f2c3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_a66aa47f-7269-4d29-a295-2d3718b9f2c3" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_a66aa47f-7269-4d29-a295-2d3718b9f2c3_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_a66aa47f-7269-4d29-a295-2d3718b9f2c3" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_a66aa47f-7269-4d29-a295-2d3718b9f2c3_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_49970b3f-4d0c-4a8c-90cf-359ee68ed1d7" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_EquityMethodInvesteeNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_a66aa47f-7269-4d29-a295-2d3718b9f2c3" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_49970b3f-4d0c-4a8c-90cf-359ee68ed1d7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PharmsynthezMember_8954bf31-837b-46bf-ba0d-ba71c468b39e" xlink:href="opk-20201231.xsd#opk_PharmsynthezMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_49970b3f-4d0c-4a8c-90cf-359ee68ed1d7" xlink:to="loc_opk_PharmsynthezMember_8954bf31-837b-46bf-ba0d-ba71c468b39e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_28f97aa8-9605-4a3c-bac0-ad749e18f5ed" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_CounterpartyNameAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_srt_CounterpartyNameAxis_28f97aa8-9605-4a3c-bac0-ad749e18f5ed" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_28f97aa8-9605-4a3c-bac0-ad749e18f5ed_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_28f97aa8-9605-4a3c-bac0-ad749e18f5ed" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_28f97aa8-9605-4a3c-bac0-ad749e18f5ed_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9a8edf95-c42f-49c8-b940-7d8b07541db1" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_28f97aa8-9605-4a3c-bac0-ad749e18f5ed" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9a8edf95-c42f-49c8-b940-7d8b07541db1" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_EirGenPharmaLimitedMember_ad915270-dcd3-4916-a121-a8ded28e5358" xlink:href="opk-20201231.xsd#opk_EirGenPharmaLimitedMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9a8edf95-c42f-49c8-b940-7d8b07541db1" xlink:to="loc_opk_EirGenPharmaLimitedMember_ad915270-dcd3-4916-a121-a8ded28e5358" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ViforFreseniusMedicalCarePharmaLtdMember_8cae16c2-b260-47a5-b1ca-344eb82b73d8" xlink:href="opk-20201231.xsd#opk_ViforFreseniusMedicalCarePharmaLtdMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9a8edf95-c42f-49c8-b940-7d8b07541db1" xlink:to="loc_opk_ViforFreseniusMedicalCarePharmaLtdMember_8cae16c2-b260-47a5-b1ca-344eb82b73d8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PfizerMember_98a68055-f1bd-4f6a-8801-5b0a48abf1ad" xlink:href="opk-20201231.xsd#opk_PfizerMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9a8edf95-c42f-49c8-b940-7d8b07541db1" xlink:to="loc_opk_PfizerMember_98a68055-f1bd-4f6a-8801-5b0a48abf1ad" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_55b002ad-3806-443a-96ea-6256613a59a6" xlink:to="loc_srt_ProductOrServiceAxis_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61" xlink:type="arc" order="6"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61" xlink:to="loc_srt_ProductsAndServicesDomain_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_7ae0a6ad-6acc-4390-8ea0-7c5af28f3d61" xlink:to="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TransferOfIntellectualPropertyAndOtherMember_003a7c04-af80-4040-b2eb-3456c4d5e05c" xlink:href="opk-20201231.xsd#opk_TransferOfIntellectualPropertyAndOtherMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_opk_TransferOfIntellectualPropertyAndOtherMember_003a7c04-af80-4040-b2eb-3456c4d5e05c" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_769396cc-2ba5-45c8-9863-5887ac4a691a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_us-gaap_ProductMember_769396cc-2ba5-45c8-9863-5887ac4a691a" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_RegulatoryMilestonesMember_4f7f8b90-4257-4b17-bb35-4ea96bd1ad45" xlink:href="opk-20201231.xsd#opk_RegulatoryMilestonesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_opk_RegulatoryMilestonesMember_4f7f8b90-4257-4b17-bb35-4ea96bd1ad45" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_SalesMilestonesMember_66287b60-127a-4e38-84af-400f257af8a5" xlink:href="opk-20201231.xsd#opk_SalesMilestonesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_opk_SalesMilestonesMember_66287b60-127a-4e38-84af-400f257af8a5" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DevelopmentandLicenseAgreementMember_6bce9532-a1b6-4d87-b4ff-56a7d87c06a2" xlink:href="opk-20201231.xsd#opk_DevelopmentandLicenseAgreementMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_opk_DevelopmentandLicenseAgreementMember_6bce9532-a1b6-4d87-b4ff-56a7d87c06a2" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ExclusiveOptionMember_95722acf-d950-41ad-a35d-4c52f13ad704" xlink:href="opk-20201231.xsd#opk_ExclusiveOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4fc1f572-2ff1-4b5e-b2a7-a052970cdf84" xlink:to="loc_opk_ExclusiveOptionMember_95722acf-d950-41ad-a35d-4c52f13ad704" xlink:type="arc" order="5"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/Leases" xlink:type="simple" xlink:href="opk-20201231.xsd#Leases"/>
<link:definitionLink xlink:role="http://www.opko.com/role/Leases" xlink:type="extended" id="if9bd02cfc0fa4157a4d2774d8f9e0e62_Leases"/>
<link:roleRef roleURI="http://www.opko.com/role/LeasesTables" xlink:type="simple" xlink:href="opk-20201231.xsd#LeasesTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/LeasesTables" xlink:type="extended" id="i92062e9383164c0282e95fc03ae87e54_LeasesTables"/>
<link:roleRef roleURI="http://www.opko.com/role/LeasesLeaseAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#LeasesLeaseAssetsandLiabilitiesDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/LeasesLeaseAssetsandLiabilitiesDetails" xlink:type="extended" id="i56cdfecba77f4d198174004573f1cdbd_LeasesLeaseAssetsandLiabilitiesDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/LeasesLeaseLiabilityMaturityDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#LeasesLeaseLiabilityMaturityDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/LeasesLeaseLiabilityMaturityDetails" xlink:type="extended" id="i36033612f22643d882b33fb97756b448_LeasesLeaseLiabilityMaturityDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#LeasesNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/LeasesNarrativeDetails" xlink:type="extended" id="i306415461f6b4a5f854429dfe24b03ec_LeasesNarrativeDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/LeasesSupplementalCashFlowInformationDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#LeasesSupplementalCashFlowInformationDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/LeasesSupplementalCashFlowInformationDetails" xlink:type="extended" id="i861cf6afaefd425b88b91c7203892ac9_LeasesSupplementalCashFlowInformationDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/Segments" xlink:type="simple" xlink:href="opk-20201231.xsd#Segments"/>
<link:definitionLink xlink:role="http://www.opko.com/role/Segments" xlink:type="extended" id="ie2bad189d6964d96a4d967690b6eeba1_Segments"/>
<link:roleRef roleURI="http://www.opko.com/role/SegmentsTables" xlink:type="simple" xlink:href="opk-20201231.xsd#SegmentsTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SegmentsTables" xlink:type="extended" id="iaf9ec4780e8546498d62736ad68a889f_SegmentsTables"/>
<link:roleRef roleURI="http://www.opko.com/role/SegmentsNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#SegmentsNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SegmentsNarrativeDetails" xlink:type="extended" id="ic7c3921d94fd49d48ffd23dcea9db314_SegmentsNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_f0812793-16e9-4259-80c0-8ee1f9e16c22" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentReportingInformationLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfReportableSegments_8c24a687-1dc3-4334-8cd3-28dad84be493" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NumberOfReportableSegments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_f0812793-16e9-4259-80c0-8ee1f9e16c22" xlink:to="loc_us-gaap_NumberOfReportableSegments_8c24a687-1dc3-4334-8cd3-28dad84be493" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_51aa0659-fc54-4bb9-bc09-dc5744d46750" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Revenues"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_f0812793-16e9-4259-80c0-8ee1f9e16c22" xlink:to="loc_us-gaap_Revenues_51aa0659-fc54-4bb9-bc09-dc5744d46750" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_1692e9bc-0b22-415c-8ab2-d2a95f901d4a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestExpense"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_f0812793-16e9-4259-80c0-8ee1f9e16c22" xlink:to="loc_us-gaap_InterestExpense_1692e9bc-0b22-415c-8ab2-d2a95f901d4a" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_abfea058-4b70-40a5-8a9b-e02957e2d884" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_f0812793-16e9-4259-80c0-8ee1f9e16c22" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_abfea058-4b70-40a5-8a9b-e02957e2d884" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsAxis_880537d7-1385-4e94-bf3f-88ad14a9f12d" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_abfea058-4b70-40a5-8a9b-e02957e2d884" xlink:to="loc_srt_ConsolidationItemsAxis_880537d7-1385-4e94-bf3f-88ad14a9f12d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_880537d7-1385-4e94-bf3f-88ad14a9f12d_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidationItemsAxis_880537d7-1385-4e94-bf3f-88ad14a9f12d" xlink:to="loc_srt_ConsolidationItemsDomain_880537d7-1385-4e94-bf3f-88ad14a9f12d_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_76de0cb3-d96c-4199-afc6-1ea4570caec3" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidationItemsAxis_880537d7-1385-4e94-bf3f-88ad14a9f12d" xlink:to="loc_srt_ConsolidationItemsDomain_76de0cb3-d96c-4199-afc6-1ea4570caec3" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntersegmentEliminationMember_6a182aba-e41e-4037-b801-f77b5460829a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IntersegmentEliminationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidationItemsDomain_76de0cb3-d96c-4199-afc6-1ea4570caec3" xlink:to="loc_us-gaap_IntersegmentEliminationMember_6a182aba-e41e-4037-b801-f77b5460829a" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/SegmentsOperationsandAssetsforOperatingSegmentsandGeographicInformationDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#SegmentsOperationsandAssetsforOperatingSegmentsandGeographicInformationDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SegmentsOperationsandAssetsforOperatingSegmentsandGeographicInformationDetails" xlink:type="extended" id="i8c48cc3cc49f4c65aeafa40b912b114f_SegmentsOperationsandAssetsforOperatingSegmentsandGeographicInformationDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentReportingInformationLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_077e229a-d914-44d7-af16-137859bfa337" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_077e229a-d914-44d7-af16-137859bfa337" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_82767a3a-f316-45f8-a4f5-2d442e31e894" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingIncomeLoss"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_OperatingIncomeLoss_82767a3a-f316-45f8-a4f5-2d442e31e894" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_129eabd9-362d-44f3-8305-b52bc750141f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_129eabd9-362d-44f3-8305-b52bc750141f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnInvestments_0a02747f-5834-4e5f-aa83-6823f575f558" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GainLossOnInvestments"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_GainLossOnInvestments_0a02747f-5834-4e5f-aa83-6823f575f558" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_fa5c90f9-3568-43ab-8124-775725c6f989" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Assets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_Assets_fa5c90f9-3568-43ab-8124-775725c6f989" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_0ca1a5d2-d28a-4e0f-9d5f-f5816b6a79d5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Goodwill"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_Goodwill_0ca1a5d2-d28a-4e0f-9d5f-f5816b6a79d5" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_05c85fb2-0602-4aae-b498-dcfc0434e2a8" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_979425a4-e370-4c1c-9d16-be1a2fe53824" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:to="loc_srt_ProductOrServiceAxis_979425a4-e370-4c1c-9d16-be1a2fe53824" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_979425a4-e370-4c1c-9d16-be1a2fe53824_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_979425a4-e370-4c1c-9d16-be1a2fe53824" xlink:to="loc_srt_ProductsAndServicesDomain_979425a4-e370-4c1c-9d16-be1a2fe53824_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_f2317116-c1ef-44cd-9125-0783bbd9c325" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductsAndServicesDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_979425a4-e370-4c1c-9d16-be1a2fe53824" xlink:to="loc_srt_ProductsAndServicesDomain_f2317116-c1ef-44cd-9125-0783bbd9c325" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_a57fbe45-2081-451e-8808-76b74e897d36" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ServiceMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2317116-c1ef-44cd-9125-0783bbd9c325" xlink:to="loc_us-gaap_ServiceMember_a57fbe45-2081-451e-8808-76b74e897d36" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_db10d7f1-8658-44e1-be3f-aa7c8542e3ee" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProductMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2317116-c1ef-44cd-9125-0783bbd9c325" xlink:to="loc_us-gaap_ProductMember_db10d7f1-8658-44e1-be3f-aa7c8542e3ee" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_TransferOfIntellectualPropertyAndOtherMember_88557042-a8fa-483e-9ba1-d7dd9c068c94" xlink:href="opk-20201231.xsd#opk_TransferOfIntellectualPropertyAndOtherMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_f2317116-c1ef-44cd-9125-0783bbd9c325" xlink:to="loc_opk_TransferOfIntellectualPropertyAndOtherMember_88557042-a8fa-483e-9ba1-d7dd9c068c94" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_bdc1faf1-39c6-44de-8c1c-01e198105c93" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_bdc1faf1-39c6-44de-8c1c-01e198105c93" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_bdc1faf1-39c6-44de-8c1c-01e198105c93_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_bdc1faf1-39c6-44de-8c1c-01e198105c93" xlink:to="loc_us-gaap_SegmentDomain_bdc1faf1-39c6-44de-8c1c-01e198105c93_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_4449d8b5-08b3-4e21-b268-ed8e37669337" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_SegmentDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_bdc1faf1-39c6-44de-8c1c-01e198105c93" xlink:to="loc_us-gaap_SegmentDomain_4449d8b5-08b3-4e21-b268-ed8e37669337" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_PharmaceuticalMember_fe48b8a0-171a-448f-bcdc-0d673e4fc849" xlink:href="opk-20201231.xsd#opk_PharmaceuticalMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_4449d8b5-08b3-4e21-b268-ed8e37669337" xlink:to="loc_opk_PharmaceuticalMember_fe48b8a0-171a-448f-bcdc-0d673e4fc849" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_DiagnosticsMember_c2e317db-f769-4fb8-ac02-1dce43005e01" xlink:href="opk-20201231.xsd#opk_DiagnosticsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_4449d8b5-08b3-4e21-b268-ed8e37669337" xlink:to="loc_opk_DiagnosticsMember_c2e317db-f769-4fb8-ac02-1dce43005e01" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsAxis_c0c2875a-a773-433f-b6a3-2eb5d4e5d198" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:to="loc_srt_ConsolidationItemsAxis_c0c2875a-a773-433f-b6a3-2eb5d4e5d198" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_c0c2875a-a773-433f-b6a3-2eb5d4e5d198_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidationItemsAxis_c0c2875a-a773-433f-b6a3-2eb5d4e5d198" xlink:to="loc_srt_ConsolidationItemsDomain_c0c2875a-a773-433f-b6a3-2eb5d4e5d198_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidationItemsDomain_b5cf98fb-69a1-48cc-8bf6-daba724986ae" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ConsolidationItemsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidationItemsAxis_c0c2875a-a773-433f-b6a3-2eb5d4e5d198" xlink:to="loc_srt_ConsolidationItemsDomain_b5cf98fb-69a1-48cc-8bf6-daba724986ae" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingSegmentsMember_dca4fceb-a0f0-4fc5-9b70-76e8720728f0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingSegmentsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidationItemsDomain_b5cf98fb-69a1-48cc-8bf6-daba724986ae" xlink:to="loc_us-gaap_OperatingSegmentsMember_dca4fceb-a0f0-4fc5-9b70-76e8720728f0" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateNonSegmentMember_cbe480c5-8b04-4332-9f26-c20a2a619c6d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CorporateNonSegmentMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidationItemsDomain_b5cf98fb-69a1-48cc-8bf6-daba724986ae" xlink:to="loc_us-gaap_CorporateNonSegmentMember_cbe480c5-8b04-4332-9f26-c20a2a619c6d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_be4fc934-4d60-4d6c-9dd5-a5a83e75992b" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_StatementGeographicalAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_5008908d-a10c-43de-8bef-891848b11d8a" xlink:to="loc_srt_StatementGeographicalAxis_be4fc934-4d60-4d6c-9dd5-a5a83e75992b" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_be4fc934-4d60-4d6c-9dd5-a5a83e75992b_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_SegmentGeographicalDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_be4fc934-4d60-4d6c-9dd5-a5a83e75992b" xlink:to="loc_srt_SegmentGeographicalDomain_be4fc934-4d60-4d6c-9dd5-a5a83e75992b_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_SegmentGeographicalDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_be4fc934-4d60-4d6c-9dd5-a5a83e75992b" xlink:to="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_country_US_defd9828-eb41-4588-a72b-00719aba9ab5" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_US"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_US_defd9828-eb41-4588-a72b-00719aba9ab5" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_country_IE_f978dfe3-61b8-45ee-b85e-8146c6d7b31d" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_IE"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_IE_f978dfe3-61b8-45ee-b85e-8146c6d7b31d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_country_CL_d77a2258-e03a-4578-a085-0789782f40a7" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_CL"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_CL_d77a2258-e03a-4578-a085-0789782f40a7" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_country_ES_497828bd-c35f-48a9-97a3-ab26f51ad467" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_ES"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_ES_497828bd-c35f-48a9-97a3-ab26f51ad467" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_country_IL_f5e3ca8b-70e6-44ad-951e-b66d8463cb06" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_IL"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_IL_f5e3ca8b-70e6-44ad-951e-b66d8463cb06" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_country_MX_7d47e881-b1a0-4398-ab19-f1960612a0da" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_MX"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_country_MX_7d47e881-b1a0-4398-ab19-f1960612a0da" xlink:type="arc" order="5"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_OtherCountriesMember_e6124e8d-43c3-45fa-93e5-f41788bbad5d" xlink:href="opk-20201231.xsd#opk_OtherCountriesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_ec674ecf-3fbe-4844-bbe8-c76fefac786e" xlink:to="loc_opk_OtherCountriesMember_e6124e8d-43c3-45fa-93e5-f41788bbad5d" xlink:type="arc" order="6"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/SegmentsPropertyPlantandEquipmentNetbyJurisdictionDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#SegmentsPropertyPlantandEquipmentNetbyJurisdictionDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SegmentsPropertyPlantandEquipmentNetbyJurisdictionDetails" xlink:type="extended" id="i1970ba7df34a474e8035162a2dac1c6d_SegmentsPropertyPlantandEquipmentNetbyJurisdictionDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_7e752ef4-7668-4546-a41e-27bfa0395cf8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_5e3af793-37e0-40b6-8fcb-c561db9ea43b" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_7e752ef4-7668-4546-a41e-27bfa0395cf8" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_5e3af793-37e0-40b6-8fcb-c561db9ea43b" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_48351154-90b9-4de1-ac8e-71d37ad571ab" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_7e752ef4-7668-4546-a41e-27bfa0395cf8" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_48351154-90b9-4de1-ac8e-71d37ad571ab" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_StatementGeographicalAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_48351154-90b9-4de1-ac8e-71d37ad571ab" xlink:to="loc_srt_StatementGeographicalAxis_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7_default" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_SegmentGeographicalDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7" xlink:to="loc_srt_SegmentGeographicalDomain_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_97b593ff-8e22-44ac-8c27-a37fc449bf82" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_SegmentGeographicalDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_b2a60ff5-91f8-4cce-bc30-522c6f3a7be7" xlink:to="loc_srt_SegmentGeographicalDomain_97b593ff-8e22-44ac-8c27-a37fc449bf82" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_country_US_db4d94d4-8189-4bfc-9d18-10f84db5d734" xlink:href="https://xbrl.sec.gov/country/2020/country-2020-01-31.xsd#country_US"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_97b593ff-8e22-44ac-8c27-a37fc449bf82" xlink:to="loc_country_US_db4d94d4-8189-4bfc-9d18-10f84db5d734" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_c10f7919-c9ee-49ac-a002-5668f267f70f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NonUsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_97b593ff-8e22-44ac-8c27-a37fc449bf82" xlink:to="loc_us-gaap_NonUsMember_c10f7919-c9ee-49ac-a002-5668f267f70f" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurements"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurements" xlink:type="extended" id="ibe67e6def9e64fe2883e1b440e2b5afc_FairValueMeasurements"/>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurementsTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurementsTables" xlink:type="extended" id="iaf2bf03da90647a8afdb4c96492efe5c_FairValueMeasurementsTables"/>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurementsFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurementsFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurementsFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails" xlink:type="extended" id="i4ec7fe1e9536463c9997ad3953a4e9a5_FairValueMeasurementsFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2e32cd40-8bc4-417d-9f56-6cff5ffffe93" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2e32cd40-8bc4-417d-9f56-6cff5ffffe93" xlink:to="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNi_d8d25c00-7089-4f59-bdac-3987160a9bb5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_EquitySecuritiesFvNi"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:to="loc_us-gaap_EquitySecuritiesFvNi_d8d25c00-7089-4f59-bdac-3987160a9bb5" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_776909be-781e-421d-86df-99fc9bb3bd36" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_776909be-781e-421d-86df-99fc9bb3bd36" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_db673e8d-e4a3-4310-b4fc-04c94df125f7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeAssets"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:to="loc_us-gaap_DerivativeAssets_db673e8d-e4a3-4310-b4fc-04c94df125f7" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_82931174-14c2-4e40-8abf-e82a117b73b9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetsFairValueDisclosure"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FinancialInstrumentsFinancialAssetsBalanceSheetGroupingsAbstract_ed56179b-d51a-4a96-a63f-22b44b4a7749" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_82931174-14c2-4e40-8abf-e82a117b73b9" xlink:type="arc" order="4"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_65c7e5d3-0924-471c-b85f-959a48ca6a13" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2e32cd40-8bc4-417d-9f56-6cff5ffffe93" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_65c7e5d3-0924-471c-b85f-959a48ca6a13" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_bbf8ef7d-3ab7-4e77-90e8-2bc0685d316c" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeLiabilities"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_65c7e5d3-0924-471c-b85f-959a48ca6a13" xlink:to="loc_us-gaap_DerivativeLiabilities_bbf8ef7d-3ab7-4e77-90e8-2bc0685d316c" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_974d0c2a-9688-4872-82dc-7aa1dc62d30f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_65c7e5d3-0924-471c-b85f-959a48ca6a13" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_974d0c2a-9688-4872-82dc-7aa1dc62d30f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_8c70327a-5484-41f3-8270-194109474bd6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_65c7e5d3-0924-471c-b85f-959a48ca6a13" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_8c70327a-5484-41f3-8270-194109474bd6" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_79d8aef8-6aa6-43b2-865f-8ac34176c011" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2e32cd40-8bc4-417d-9f56-6cff5ffffe93" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_79d8aef8-6aa6-43b2-865f-8ac34176c011" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_cb9d4a46-572c-43df-b680-e224425d6751" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_79d8aef8-6aa6-43b2-865f-8ac34176c011" xlink:to="loc_us-gaap_FinancialInstrumentAxis_cb9d4a46-572c-43df-b680-e224425d6751" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_cb9d4a46-572c-43df-b680-e224425d6751_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_cb9d4a46-572c-43df-b680-e224425d6751" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_cb9d4a46-572c-43df-b680-e224425d6751_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d4090843-a47c-4045-a720-831e7637e595" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_cb9d4a46-572c-43df-b680-e224425d6751" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d4090843-a47c-4045-a720-831e7637e595" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_6752196f-2b0d-48af-b554-d0b431a1ea62" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForwardContractsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_d4090843-a47c-4045-a720-831e7637e595" xlink:to="loc_us-gaap_ForwardContractsMember_6752196f-2b0d-48af-b554-d0b431a1ea62" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_79d8aef8-6aa6-43b2-865f-8ac34176c011" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_d227e6ce-e04c-4507-aca9-07c3ef97213d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_c4314fd7-2ff5-4d13-9c5d-acfdfafe4e1f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_d227e6ce-e04c-4507-aca9-07c3ef97213d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_c1c82b2a-5b7b-47d1-9c02-12e0d25b9013" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_d227e6ce-e04c-4507-aca9-07c3ef97213d" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_c1c82b2a-5b7b-47d1-9c02-12e0d25b9013" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_e9674bf7-9393-4d7c-a65f-2e063b78b8bc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_d227e6ce-e04c-4507-aca9-07c3ef97213d" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_e9674bf7-9393-4d7c-a65f-2e063b78b8bc" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_c5177876-bf1d-4a89-9913-05caab6288e6" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel3Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_d227e6ce-e04c-4507-aca9-07c3ef97213d" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_c5177876-bf1d-4a89-9913-05caab6288e6" xlink:type="arc" order="2"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurementsCarryingAmountandEstimatedFairValueofLongTermDebtDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurementsCarryingAmountandEstimatedFairValueofLongTermDebtDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurementsCarryingAmountandEstimatedFairValueofLongTermDebtDetails" xlink:type="extended" id="ice1c46875f3444e1ab26ccfc6d3172b6_FairValueMeasurementsCarryingAmountandEstimatedFairValueofLongTermDebtDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_05b0a48a-f937-4e1e-9338-fb1fc0a7f37f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayableFairValueDisclosure_d92f14a4-3da3-4e9f-86df-8cd7c14788ea" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NotesPayableFairValueDisclosure"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_05b0a48a-f937-4e1e-9338-fb1fc0a7f37f" xlink:to="loc_us-gaap_NotesPayableFairValueDisclosure_d92f14a4-3da3-4e9f-86df-8cd7c14788ea" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByBalanceSheetGroupingTable_f2c36567-c7ec-4eb1-94b2-39d5e012f7df" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByBalanceSheetGroupingTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_05b0a48a-f937-4e1e-9338-fb1fc0a7f37f" xlink:to="loc_us-gaap_FairValueByBalanceSheetGroupingTable_f2c36567-c7ec-4eb1-94b2-39d5e012f7df" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_209d6468-c0b2-40af-9744-5b0f40c98381" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_f2c36567-c7ec-4eb1-94b2-39d5e012f7df" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_209d6468-c0b2-40af-9744-5b0f40c98381" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_209d6468-c0b2-40af-9744-5b0f40c98381_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_209d6468-c0b2-40af-9744-5b0f40c98381" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_209d6468-c0b2-40af-9744-5b0f40c98381_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_94b3315d-a9c7-4f12-a14d-8236598edcb7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_209d6468-c0b2-40af-9744-5b0f40c98381" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_94b3315d-a9c7-4f12-a14d-8236598edcb7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_724f7ceb-1c8d-454f-bee7-85c6d5533428" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_94b3315d-a9c7-4f12-a14d-8236598edcb7" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_724f7ceb-1c8d-454f-bee7-85c6d5533428" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_33ea28c9-2412-4005-88a9-2b948068f9c7" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_94b3315d-a9c7-4f12-a14d-8236598edcb7" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_33ea28c9-2412-4005-88a9-2b948068f9c7" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_a92815fa-2cf4-448b-8e48-57de5aa439ef" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueInputsLevel3Member"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_94b3315d-a9c7-4f12-a14d-8236598edcb7" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_a92815fa-2cf4-448b-8e48-57de5aa439ef" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementBasisAxis_319d3cc6-5925-4ad4-8153-fa2d74d476c2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByMeasurementBasisAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_f2c36567-c7ec-4eb1-94b2-39d5e012f7df" xlink:to="loc_us-gaap_FairValueByMeasurementBasisAxis_319d3cc6-5925-4ad4-8153-fa2d74d476c2" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_319d3cc6-5925-4ad4-8153-fa2d74d476c2_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementBasisAxis_319d3cc6-5925-4ad4-8153-fa2d74d476c2" xlink:to="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_319d3cc6-5925-4ad4-8153-fa2d74d476c2_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueDisclosureItemAmountsDomain_b3fc5db1-5fa3-4491-b32a-668c7d792bc9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueDisclosureItemAmountsDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementBasisAxis_319d3cc6-5925-4ad4-8153-fa2d74d476c2" xlink:to="loc_us-gaap_FairValueDisclosureItemAmountsDomain_b3fc5db1-5fa3-4491-b32a-668c7d792bc9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_1f360f04-ff09-46a7-a24c-261d9cefc4a5" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueDisclosureItemAmountsDomain_b3fc5db1-5fa3-4491-b32a-668c7d792bc9" xlink:to="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_1f360f04-ff09-46a7-a24c-261d9cefc4a5" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_CarryingReportedAmountFairValueDisclosureMember_73749fc6-f847-41f8-978e-99771b91174e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CarryingReportedAmountFairValueDisclosureMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueDisclosureItemAmountsDomain_b3fc5db1-5fa3-4491-b32a-668c7d792bc9" xlink:to="loc_us-gaap_CarryingReportedAmountFairValueDisclosureMember_73749fc6-f847-41f8-978e-99771b91174e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_c0a43a86-7cd2-4566-9ef9-771ecae4e84a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_f2c36567-c7ec-4eb1-94b2-39d5e012f7df" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_c0a43a86-7cd2-4566-9ef9-771ecae4e84a" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_c0a43a86-7cd2-4566-9ef9-771ecae4e84a_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_c0a43a86-7cd2-4566-9ef9-771ecae4e84a" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_c0a43a86-7cd2-4566-9ef9-771ecae4e84a_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_2aa924b1-7add-4417-a769-4ef6b52cbf0e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongtermDebtTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_c0a43a86-7cd2-4566-9ef9-771ecae4e84a" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_2aa924b1-7add-4417-a769-4ef6b52cbf0e" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_c9524421-20d3-44bc-92a9-4cedaba111fb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ConvertibleNotesPayableMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_2aa924b1-7add-4417-a769-4ef6b52cbf0e" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_c9524421-20d3-44bc-92a9-4cedaba111fb" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurementsReconciliationofBeginningandEndingBalancesofLevel3AssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurementsReconciliationofBeginningandEndingBalancesofLevel3AssetsandLiabilitiesDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurementsReconciliationofBeginningandEndingBalancesofLevel3AssetsandLiabilitiesDetails" xlink:type="extended" id="i198d965c9eb4453093044ffa222282aa_FairValueMeasurementsReconciliationofBeginningandEndingBalancesofLevel3AssetsandLiabilitiesDetails">
<link:loc xlink:type="locator" xlink:label="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationLineItems_63c92d4e-8087-4288-9284-4bccd0887b77" xlink:href="opk-20201231.xsd#opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_638faf18-4b4e-46c4-a05b-016f14dd0f7d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationLineItems_63c92d4e-8087-4288-9284-4bccd0887b77" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_638faf18-4b4e-46c4-a05b-016f14dd0f7d" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_FairValueMeasurementwithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossAbstract_c07e1f99-b1e2-4c6a-9997-151ba48b0495" xlink:href="opk-20201231.xsd#opk_FairValueMeasurementwithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossAbstract"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward_638faf18-4b4e-46c4-a05b-016f14dd0f7d" xlink:to="loc_opk_FairValueMeasurementwithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossAbstract_c07e1f99-b1e2-4c6a-9997-151ba48b0495" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_b88f8851-cdc0-4ce9-82a6-48a3a4204d53" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_FairValueMeasurementwithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossAbstract_c07e1f99-b1e2-4c6a-9997-151ba48b0495" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_b88f8851-cdc0-4ce9-82a6-48a3a4204d53" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_f940d60f-7324-41fe-9573-1b5cff8495c0" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_opk_FairValueMeasurementwithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossAbstract_c07e1f99-b1e2-4c6a-9997-151ba48b0495" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_f940d60f-7324-41fe-9573-1b5cff8495c0" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue_c637939b-e885-48fb-9879-ecd6dde92879" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationsRecurringBasisLiabilityValue"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationTable_af5d79af-465c-45fa-a337-efb8ca21d648" xlink:href="opk-20201231.xsd#opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationLineItems_63c92d4e-8087-4288-9284-4bccd0887b77" xlink:to="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationTable_af5d79af-465c-45fa-a337-efb8ca21d648" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByLiabilityClassAxis_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueByLiabilityClassAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_opk_FairValueAssetsAndLiabilitiesMeasuredonRecurringBasisUnobservableInputReconciliationTable_af5d79af-465c-45fa-a337-efb8ca21d648" xlink:to="loc_us-gaap_FairValueByLiabilityClassAxis_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_7f6e15c0-afd9-440e-af31-d457a1640f4d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByLiabilityClassAxis_e4ea8fc6-a3f4-4172-aec8-cc3e21828f53" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_7f6e15c0-afd9-440e-af31-d457a1640f4d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_ContingentConsiderationMember_bcc0048a-5be0-47c4-8e57-99bc207404f4" xlink:href="opk-20201231.xsd#opk_ContingentConsiderationMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationByLiabilityClassDomain_7f6e15c0-afd9-440e-af31-d457a1640f4d" xlink:to="loc_opk_ContingentConsiderationMember_bcc0048a-5be0-47c4-8e57-99bc207404f4" xlink:type="arc" order="0"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#FairValueMeasurementsNarrativeDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="extended" id="i79a0e2e32d9b49859c0aa791ad33b6ee_FairValueMeasurementsNarrativeDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_894f954c-ab7b-4cd4-97a3-0537660eae9a" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_837e9adc-e1eb-485a-abf9-ba2fa75a5a00" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_894f954c-ab7b-4cd4-97a3-0537660eae9a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_837e9adc-e1eb-485a-abf9-ba2fa75a5a00" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_f436957b-3dac-4405-96e3-757d686e66ec" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_894f954c-ab7b-4cd4-97a3-0537660eae9a" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_f436957b-3dac-4405-96e3-757d686e66ec" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_4764737a-4657-4df7-a2f4-965906ba92b8" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_f436957b-3dac-4405-96e3-757d686e66ec" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_4764737a-4657-4df7-a2f4-965906ba92b8" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_4764737a-4657-4df7-a2f4-965906ba92b8_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_4764737a-4657-4df7-a2f4-965906ba92b8" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_4764737a-4657-4df7-a2f4-965906ba92b8_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_e8603d73-972e-4a3a-99a7-adee790c482d" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_4764737a-4657-4df7-a2f4-965906ba92b8" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_e8603d73-972e-4a3a-99a7-adee790c482d" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesMember_964b4315-cd36-4c22-b7ce-a560709f2275" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_e8603d73-972e-4a3a-99a7-adee790c482d" xlink:to="loc_us-gaap_AccruedLiabilitiesMember_964b4315-cd36-4c22-b7ce-a560709f2275" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNoncurrentLiabilitiesMember_1f1a2cc5-e41c-473e-9496-977483f2f8cb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNoncurrentLiabilitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_e8603d73-972e-4a3a-99a7-adee790c482d" xlink:to="loc_us-gaap_OtherNoncurrentLiabilitiesMember_1f1a2cc5-e41c-473e-9496-977483f2f8cb" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DerivativeContracts" xlink:type="simple" xlink:href="opk-20201231.xsd#DerivativeContracts"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DerivativeContracts" xlink:type="extended" id="i03f79674752a43f1a3198c0ebbfafde1_DerivativeContracts"/>
<link:roleRef roleURI="http://www.opko.com/role/DerivativeContractsTables" xlink:type="simple" xlink:href="opk-20201231.xsd#DerivativeContractsTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DerivativeContractsTables" xlink:type="extended" id="i398136a261464c388a7ba1aefe7176e6_DerivativeContractsTables"/>
<link:roleRef roleURI="http://www.opko.com/role/DerivativeContractsSummaryofFairValuesandPresentationofDerivativeFinancialInstrumentsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DerivativeContractsSummaryofFairValuesandPresentationofDerivativeFinancialInstrumentsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DerivativeContractsSummaryofFairValuesandPresentationofDerivativeFinancialInstrumentsDetails" xlink:type="extended" id="i1e8392b62c854808bcabc1b33bcb2ea6_DerivativeContractsSummaryofFairValuesandPresentationofDerivativeFinancialInstrumentsDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativesFairValueLineItems_aed0fc95-5980-4646-bcc9-7b4319437921" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativesFairValueLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_7bae393e-402a-401a-b4b3-ca5acbcc92dc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeAsset"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativesFairValueLineItems_aed0fc95-5980-4646-bcc9-7b4319437921" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeAsset_7bae393e-402a-401a-b4b3-ca5acbcc92dc" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeFairValueOfDerivativeLiability_c4815c09-8837-48cc-9419-827695fa3e90" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeFairValueOfDerivativeLiability"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativesFairValueLineItems_aed0fc95-5980-4646-bcc9-7b4319437921" xlink:to="loc_us-gaap_DerivativeFairValueOfDerivativeLiability_c4815c09-8837-48cc-9419-827695fa3e90" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable_3b2dfe31-f90c-4d17-a3a7-b042facdef77" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativesFairValueLineItems_aed0fc95-5980-4646-bcc9-7b4319437921" xlink:to="loc_us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable_3b2dfe31-f90c-4d17-a3a7-b042facdef77" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_aeca88da-4631-4679-a3e8-c32eb73a08e9" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable_3b2dfe31-f90c-4d17-a3a7-b042facdef77" xlink:to="loc_us-gaap_HedgingDesignationAxis_aeca88da-4631-4679-a3e8-c32eb73a08e9" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_aeca88da-4631-4679-a3e8-c32eb73a08e9_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_aeca88da-4631-4679-a3e8-c32eb73a08e9" xlink:to="loc_us-gaap_HedgingDesignationDomain_aeca88da-4631-4679-a3e8-c32eb73a08e9_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_0e174672-cf21-4209-b995-b52d0f8e417f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_aeca88da-4631-4679-a3e8-c32eb73a08e9" xlink:to="loc_us-gaap_HedgingDesignationDomain_0e174672-cf21-4209-b995-b52d0f8e417f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_1b13fdb5-9170-4258-9cfc-1754d826e32f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NondesignatedMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_0e174672-cf21-4209-b995-b52d0f8e417f" xlink:to="loc_us-gaap_NondesignatedMember_1b13fdb5-9170-4258-9cfc-1754d826e32f" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_83346258-dc8a-4d8f-aeeb-c1fa81c271fb" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable_3b2dfe31-f90c-4d17-a3a7-b042facdef77" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_83346258-dc8a-4d8f-aeeb-c1fa81c271fb" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_83346258-dc8a-4d8f-aeeb-c1fa81c271fb_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_83346258-dc8a-4d8f-aeeb-c1fa81c271fb" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_83346258-dc8a-4d8f-aeeb-c1fa81c271fb_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_89a23771-a5ec-4eff-8a36-616b7c2de6db" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_83346258-dc8a-4d8f-aeeb-c1fa81c271fb" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_89a23771-a5ec-4eff-8a36-616b7c2de6db" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockOptionMember_57a2c0e1-9bac-4e6c-8fd9-a8d6ebcba6bc" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_89a23771-a5ec-4eff-8a36-616b7c2de6db" xlink:to="loc_us-gaap_StockOptionMember_57a2c0e1-9bac-4e6c-8fd9-a8d6ebcba6bc" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_8918c212-b96b-414d-a840-b36763aaf993" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForwardContractsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_89a23771-a5ec-4eff-8a36-616b7c2de6db" xlink:to="loc_us-gaap_ForwardContractsMember_8918c212-b96b-414d-a840-b36763aaf993" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_c4fc8953-4a97-42f1-9ddf-9327c1b45177" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValuesDerivativesBalanceSheetLocationByDerivativeContractTypeByHedgingDesignationTable_3b2dfe31-f90c-4d17-a3a7-b042facdef77" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_c4fc8953-4a97-42f1-9ddf-9327c1b45177" xlink:type="arc" order="3"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_c4fc8953-4a97-42f1-9ddf-9327c1b45177_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_c4fc8953-4a97-42f1-9ddf-9327c1b45177" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_c4fc8953-4a97-42f1-9ddf-9327c1b45177_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_a0804f7d-2c3d-42e4-ae07-87bc5e271174" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_c4fc8953-4a97-42f1-9ddf-9327c1b45177" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_a0804f7d-2c3d-42e4-ae07-87bc5e271174" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsMember_61e8ebbd-5625-42bc-aacf-c9946a157e69" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InvestmentsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_a0804f7d-2c3d-42e4-ae07-87bc5e271174" xlink:to="loc_us-gaap_InvestmentsMember_61e8ebbd-5625-42bc-aacf-c9946a157e69" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_opk_LongtermDebtCurrentMaturitiesMember_d57c01d2-296d-4cbd-9e53-2ca2903b1d10" xlink:href="opk-20201231.xsd#opk_LongtermDebtCurrentMaturitiesMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_a0804f7d-2c3d-42e4-ae07-87bc5e271174" xlink:to="loc_opk_LongtermDebtCurrentMaturitiesMember_d57c01d2-296d-4cbd-9e53-2ca2903b1d10" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/DerivativeContractsSummaryoftheLossesandGainsRecordedfortheChangesinFairValuesofDerivativeInstrumentsDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#DerivativeContractsSummaryoftheLossesandGainsRecordedfortheChangesinFairValuesofDerivativeInstrumentsDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/DerivativeContractsSummaryoftheLossesandGainsRecordedfortheChangesinFairValuesofDerivativeInstrumentsDetails" xlink:type="extended" id="iee3d69842a2143919850ff4bd22ecddd_DerivativeContractsSummaryoftheLossesandGainsRecordedfortheChangesinFairValuesofDerivativeInstrumentsDetails">
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsGainLossLineItems_ef03c5fe-e733-4999-b253-8278de63040f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeInstrumentsGainLossLineItems"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeGainLossOnDerivativeNet_5d5cd31c-0904-4696-a115-dfc23dbed7af" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeGainLossOnDerivativeNet"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossLineItems_ef03c5fe-e733-4999-b253-8278de63040f" xlink:to="loc_us-gaap_DerivativeGainLossOnDerivativeNet_5d5cd31c-0904-4696-a115-dfc23dbed7af" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipByIncomeStatementLocationByDerivativeInstrumentRiskTable_4f27b341-26c2-44e3-a7be-a6d5be6a5154" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipByIncomeStatementLocationByDerivativeInstrumentRiskTable"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossLineItems_ef03c5fe-e733-4999-b253-8278de63040f" xlink:to="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipByIncomeStatementLocationByDerivativeInstrumentRiskTable_4f27b341-26c2-44e3-a7be-a6d5be6a5154" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationAxis_6d49d5ed-fb70-42ad-b885-e60cff42ad4f" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipByIncomeStatementLocationByDerivativeInstrumentRiskTable_4f27b341-26c2-44e3-a7be-a6d5be6a5154" xlink:to="loc_us-gaap_HedgingDesignationAxis_6d49d5ed-fb70-42ad-b885-e60cff42ad4f" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_6d49d5ed-fb70-42ad-b885-e60cff42ad4f_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_HedgingDesignationAxis_6d49d5ed-fb70-42ad-b885-e60cff42ad4f" xlink:to="loc_us-gaap_HedgingDesignationDomain_6d49d5ed-fb70-42ad-b885-e60cff42ad4f_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_HedgingDesignationDomain_cea2e0ba-ef8c-4e40-af84-e2361a7da480" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_HedgingDesignationDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_HedgingDesignationAxis_6d49d5ed-fb70-42ad-b885-e60cff42ad4f" xlink:to="loc_us-gaap_HedgingDesignationDomain_cea2e0ba-ef8c-4e40-af84-e2361a7da480" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_NondesignatedMember_8e26b19f-fa8d-483b-a01c-c4872287cd12" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NondesignatedMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_HedgingDesignationDomain_cea2e0ba-ef8c-4e40-af84-e2361a7da480" xlink:to="loc_us-gaap_NondesignatedMember_8e26b19f-fa8d-483b-a01c-c4872287cd12" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_d359a4c5-9d98-49f9-865d-53a70102c1a2" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeInstrumentsGainLossByHedgingRelationshipByIncomeStatementLocationByDerivativeInstrumentRiskTable_4f27b341-26c2-44e3-a7be-a6d5be6a5154" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_d359a4c5-9d98-49f9-865d-53a70102c1a2" xlink:type="arc" order="2"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_d359a4c5-9d98-49f9-865d-53a70102c1a2_default" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_d359a4c5-9d98-49f9-865d-53a70102c1a2" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_d359a4c5-9d98-49f9-865d-53a70102c1a2_default" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_1a9dd531-9665-4a5b-a300-c6343f4e0078" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DerivativeContractTypeDomain"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_d359a4c5-9d98-49f9-865d-53a70102c1a2" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_1a9dd531-9665-4a5b-a300-c6343f4e0078" xlink:type="arc" order="1"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockOptionMember_25351d3b-bdd3-446e-9742-73be9a545a4e" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockOptionMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_1a9dd531-9665-4a5b-a300-c6343f4e0078" xlink:to="loc_us-gaap_StockOptionMember_25351d3b-bdd3-446e-9742-73be9a545a4e" xlink:type="arc" order="0"/>
<link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForwardContractsMember_de0209c6-fc7a-453d-bd72-daa19c362033" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ForwardContractsMember"/>
<link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_1a9dd531-9665-4a5b-a300-c6343f4e0078" xlink:to="loc_us-gaap_ForwardContractsMember_de0209c6-fc7a-453d-bd72-daa19c362033" xlink:type="arc" order="1"/>
</link:definitionLink>
<link:roleRef roleURI="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnaudited" xlink:type="simple" xlink:href="opk-20201231.xsd#SelectedQuarterlyFinancialDataUnaudited"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnaudited" xlink:type="extended" id="i7ed1df7ce4c8488aa696bbf35f22f09f_SelectedQuarterlyFinancialDataUnaudited"/>
<link:roleRef roleURI="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnauditedTables" xlink:type="simple" xlink:href="opk-20201231.xsd#SelectedQuarterlyFinancialDataUnauditedTables"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnauditedTables" xlink:type="extended" id="ibdb31899cee941b29095d0e290fffb59_SelectedQuarterlyFinancialDataUnauditedTables"/>
<link:roleRef roleURI="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnauditedSummaryofSelectedQuarterlyFinancialDataUnauditedDetails" xlink:type="simple" xlink:href="opk-20201231.xsd#SelectedQuarterlyFinancialDataUnauditedSummaryofSelectedQuarterlyFinancialDataUnauditedDetails"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SelectedQuarterlyFinancialDataUnauditedSummaryofSelectedQuarterlyFinancialDataUnauditedDetails" xlink:type="extended" id="ie41c2580aa004a7bb12142f657a8555c_SelectedQuarterlyFinancialDataUnauditedSummaryofSelectedQuarterlyFinancialDataUnauditedDetails"/>
<link:roleRef roleURI="http://www.opko.com/role/SubsequentEvents" xlink:type="simple" xlink:href="opk-20201231.xsd#SubsequentEvents"/>
<link:definitionLink xlink:role="http://www.opko.com/role/SubsequentEvents" xlink:type="extended" id="id5f9812c9c574389acfda8d26cee5e4d_SubsequentEvents"/>
</link:linkbase>

4 Subsequent Filings that Reference this Filing

  As Of               Filer                 Filing    For·On·As Docs:Size             Issuer                      Filing Agent

 3/01/24  Opko Health, Inc.                 10-K       12/31/23  122:18M                                    RDG Filings/FA
 5/15/23  Opko Health, Inc.                 S-8         5/15/23    4:98K                                    RDG Filings/FA
 2/27/23  Opko Health, Inc.                 10-K       12/31/22  121:20M
 3/01/22  Opko Health, Inc.                 10-K       12/31/21  110:16M

46 Previous Filings that this Filing References

  As Of               Filer                 Filing    For·On·As Docs:Size             Issuer                      Filing Agent

 7/31/20  Opko Health, Inc.                 10-Q        6/30/20   83:13M
 3/02/20  Opko Health, Inc.                 10-K       12/31/19  111:16M
11/05/19  Opko Health, Inc.                 10-Q        9/30/19   82:10M
10/29/19  Opko Health, Inc.                 8-K®:1,9   10/24/19   12:415K                                   Donnelley … Solutions/FA
 6/21/19  Opko Health, Inc.                 8-K:5,7,9   6/20/19    2:88K
 5/08/19  Opko Health, Inc.                 10-Q        3/31/19   82:9.6M
 3/01/19  Opko Health, Inc.                 10-K       12/31/18  112:17M
 2/07/19  Opko Health, Inc.                 8-K:1,2,3,9 2/04/19    7:1.1M                                   Donnelley … Solutions/FA
 8/07/18  Opko Health, Inc.                 10-Q        6/30/18   77:9.3M
 3/01/18  Opko Health, Inc.                 10-K       12/31/17  111:16M
11/08/17  Opko Health, Inc.                 10-Q        9/30/17   75:8.9M
10/12/17  Opko Health, Inc.                 8-K:1,9    10/12/17    2:34K                                    Donnelley … Solutions/FA
 3/23/17  Opko Health, Inc.                 8-K:1,2,9   3/17/17    2:52K                                    Donnelley … Solutions/FA
 8/08/16  Opko Health, Inc.                 10-Q        6/30/16   80:10M
 6/30/16  Opko Health, Inc.                 8-K:1,3,7,9 6/29/16    3:580K                                   Donnelley … Solutions/FA
 3/25/16  Opko Health, Inc.                 DEF 14A     5/05/16    1:498K                                   Donnelley … Solutions/FA
 2/29/16  Opko Health, Inc.                 10-K       12/31/15  116:17M
 8/05/15  Opko Health, Inc.                 10-Q        6/30/15   80:10M
 6/04/15  Opko Health, Inc.                 8-K:1,7,9   6/03/15    3:712K                                   Donnelley … Solutions/FA
 2/27/15  Opko Health, Inc.                 10-K       12/31/14  109:23M
11/12/13  Opko Health, Inc.                 10-Q        9/30/13   76:14M
 6/27/13  Opko Health, Inc.                 S-4                    6:3M                                     Donnelley … Solutions/FA
 5/10/13  Opko Health, Inc.                 10-Q        3/31/13   76:9.1M                                   Donnelley … Solutions/FA
 3/22/13  Opko Health, Inc.                 SC 13D                 2:350K Phio Pharmaceuticals Corp.        Donnelley … Solutions/FA
 3/18/13  Opko Health, Inc.                 10-K       12/31/12  111:15M                                    Donnelley … Solutions/FA
 2/05/13  Opko Health, Inc.                 8-K:1,2,3,8 1/30/13    3:751K                                   Donnelley … Solutions/FA
 1/29/13  Opko Health, Inc.                 8-K:1,2,3,8 1/23/13    4:331K                                   Donnelley … Solutions/FA
11/09/12  Opko Health, Inc.                 10-Q        9/30/12   60:6.7M                                   Donnelley … Solutions/FA
 5/10/12  Opko Health, Inc.                 10-Q        3/31/12   33:2.5M                                   Donnelley … Solutions/FA
 3/15/12  Opko Health, Inc.                 10-K       12/31/11   45:5.5M                                   Donnelley … Solutions/FA
11/09/11  Opko Health, Inc.                 10-Q        9/30/11   34:2.7M                                   Donnelley … Solutions/FA
 7/28/11  Opko Health, Inc.                 10-K/A     12/31/10    4:393K                                   Donnelley … Solutions/FA
 7/05/11  Opko Health, Inc.                 10-Q/A      3/31/11    4:164K                                   Donnelley … Solutions/FA
 5/10/11  Opko Health, Inc.                 10-Q        3/31/11    8:488K                                   Donnelley … Solutions/FA
 3/10/11  Opko Health, Inc.                 8-K:1,7,9   3/09/11    4:215K                                   Donnelley … Solutions/FA
 2/03/11  Opko Health, Inc.                 10-K/A     12/31/09    7:1M                                     Donnelley … Solutions/FA
 5/10/10  Opko Health, Inc.                 10-Q        3/31/10    6:396K                                   Donnelley … Solutions/FA
 3/17/10  Opko Health, Inc.                 10-K       12/31/09    9:1.1M                                   Donnelley … Solutions/FA
11/09/09  Opko Health, Inc.                 10-Q        9/30/09    7:373K                                   Donnelley … Solutions/FA
 9/24/09  Opko Health, Inc.                 8-K:1,3,5,8 9/18/09    6:2.7M                                   Donnelley … Solutions/FA
 8/07/09  Opko Health, Inc.                 10-Q        6/30/09    7:332K                                   Donnelley … Solutions/FA
 5/08/09  Opko Health, Inc.                 10-Q        3/31/09    7:237K                                   Bowne of Atlanta Inc./FA
11/12/08  Opko Health, Inc.                 10-Q        9/30/08    6:269K                                   Bowne of Atlanta Inc./FA
 8/08/08  Opko Health, Inc.                 10-Q        6/30/08    8:1M                                     Toppan Merrill/FA
 3/31/08  Opko Health, Inc.                 10-K       12/31/07   13:2.7M                                   Toppan Merrill/FA
 4/02/07  Opko Health, Inc.                 8-K:1,2,3,5 3/27/07   20:2M                                     Bowne of Atlanta Inc./FA
↑Top
Filing Submission 0000944809-21-000015   –   Alternative Formats (Word / Rich Text, HTML, Plain Text, et al.)
Copyright © 2024 Fran Finnegan & Company LLC – All Rights Reserved.
About — Privacy — Redactions — Help — Wed., May 15, 1:23:12.4pm ET