| Exhibit Number | | | Exhibit Description | | | Filed with this report | | | Incorporated by Reference herein from—Form or Schedule | | | Filing Date/ Period Covered | | | SEC File/Reg. Number | | |
| 10.27 | | | Employment Agreement, dated as of August 27, 2012, between Vertex Pharmaceuticals Incorporated and Stuart Arbuckle.* | | | | | | 10-Q (Exhibit 10.1) | | | November 6, 2012 | | | 000-19319 | | |
| 10.28 | | | Change of Control Agreement, dated as of August 27, 2012, between Vertex Pharmaceuticals Incorporated and Stuart Arbuckle.* | | | | | | 10-Q (Exhibit 10.2) | | | November 6, 2012 | | | 000-19319 | | |
| 10.29 | | | Employment Agreement, dated as of December 12, 2014, between Vertex Pharmaceuticals Incorporated and David Altshuler.* | | | | | | 10-K (Exhibit 10.34) | | | February 16, 2016 | | | 000-19319 | | |
| 10.30 | | | Change of Control Agreement, dated as of December 10, 2014, between Vertex Pharmaceuticals Incorporated and David Altshuler.* | | | | | | 10-K (Exhibit 10.35) | | | February 16, 2016 | | | 000-19319 | | |
| 10.31 | | | Employment Agreement, dated as of November 14, 2015, between Vertex Pharmaceuticals Incorporated and Michael Parini.* | | | | | | 10-K (Exhibit 10.40) | | | February 23, 2017 | | | 000-19319 | | |
| 10.32 | | | Change of Control Agreement, dated as of November 9, 2015, between Vertex Pharmaceuticals Incorporated and Michael Parini.* | | | | | | 10-K (Exhibit 10.41) | | | February 23, 2017 | | | 000-19319 | | |
| 10.33 | | | Third Amended and Restated Employment Agreement, dated as of February 26, 2013, between Vertex Pharmaceuticals Incorporated and Amit Sachdev.* | | | | | | 10-K (Exhibit 10.42) | | | February 23, 2017 | | | 000-19319 | | |
| 10.34 | | | Third Amended and Restated Change of Control Agreement, dated as of February 26, 2013, between Vertex Pharmaceuticals Incorporated and Amit Sachdev.* | | | | | | 10-K (Exhibit 10.43) | | | February 23, 2017 | | | 000-19319 | | |
| 10.35 | | | Employment Agreement, dated March 28, 2019, by and between Vertex Pharmaceuticals Incorporated and Charles F. Wagner, Jr.* | | | | | | 10-Q (Exhibit 10.1) | | | May 1, 2019 | | | 000-19319 | | |
| 10.36 | | | Change of Control Agreement, dated as of March 28, 2019, by and between Vertex Pharmaceuticals Incorporated and Charles F. Wagner, Jr.* | | | | | | 10-Q (Exhibit 10.2) | | | May 1, 2019 | | | 000-19319 | | |
| 10.37 | | | Amended and Restated Change of Control Agreement, dated as of May 18, 2012, between Vertex Pharmaceuticals Incorporated and Paul M. Silva.* | | | | | | 10-K (Exhibit 10.35) | | | February 13, 2020 | | | 000-19319 | | |
| 10.38 | | | Amended and Restated Employment Agreement, dated as of November 8, 2004, between Vertex Pharmaceuticals Incorporated and Ian F. Smith.* | | | | | | 10-Q (Exhibit 10.13) | | | November 4, 2009 | | | 000-19319 | | |
| 10.39 | | | Amendment No. 1 to Amended and Restated Employment Agreement between Ian F. Smith and Vertex Pharmaceuticals Incorporated, dated December 29, 2008.* | | | | | | 10-K (Exhibit 10.66) | | | February 17, 2009 | | | 000-19319 | | |
| 10.40 | | | Vertex Employee Compensation Plan.* | | | | | | 10-K (Exhibit 10.46) | | | February 15, 2018 | | | 000-19319 | | |
| 10.41 | | | Vertex Pharmaceuticals Non-Employee Board Compensation.* | | | X | | | | | | | | | | | |
| Subsidiaries | | | | | | | | | | | | | | | | | |
| 21.1 | | | Subsidiaries of Vertex Pharmaceuticals Incorporated. | | | X | | | | | | | | | | | |
| Consent | | | | | | | | | | | | | | | | | |
| 23.1 | | | Consent of Independent Registered Public Accounting Firm, Ernst & Young LLP. | | | X | | | | | | | | | | | |
| Certifications | | | | | | | | | | | | | | | | | |
| 31.1 | | | Certification of the Chief Executive Officer under Section 302 of the Sarbanes-Oxley Act of 2002. | | | X | | | | | | | | | | | |
| 31.2 | | | Certification of the Chief Financial Officer under Section 302 of the Sarbanes-Oxley Act of 2002. | | | X | | | | | | | | | | | |
| 32.1 | | | Certification of the Chief Executive Officer and the Chief Financial Officer under Section 906 of the Sarbanes-Oxley Act of 2002. | | | X | | | | | | | | | | | |
| 101.INS | | | XBRL Instance | | | X | | | | | | | | | | | |
| 101.SCH | | | XBRL Taxonomy Extension Schema | | | X | | | | | | | | | | | |
| 101.CAL | | | XBRL Taxonomy Extension Calculation | | | X | | | | | | | | | | | |
| 101.LAB | | | XBRL Taxonomy Extension Labels | | | X | | | | | | | | | | | |
| 101.PRE | | | XBRL Taxonomy Extension Presentation | | | X | | | | | | | | | | | |
| 101.DEF | | | XBRL Taxonomy Extension Definition | | | X | | | | | | | | | | | |
| 104 | | | Cover Page Interactive Data File––the cover page interactive data file does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document. | | | X | | | | | | | | | | | |