<Page>
                                                                    EXHIBIT 18.1

November 14, 2001

Board of Directors
Vertex Pharmaceuticals Incorporated
130 Waverly Street
Cambridge, Massachusetts 02139-4242

Dear Directors:

We are providing this letter to you for inclusion as an exhibit to your
Form 10-Q filing pursuant to Item 601 of Regulation S-K.

We have been provided a copy of the Company's Quarterly Report on Form 10-Q for
the period ended September 30, 2001. Footnote 3 therein describes a change in
accounting principle from recognizing collaborative and other research and
development revenue pursuant to the method described as the EITF 91-6 method to
the substantive milestone method. It should be understood that the preferability
of one acceptable method of accounting over another for revenue recognition for
those types of revenues has not been addressed in any authoritative accounting
literature and, in expressing our concurrence below, we have relied on
management's determination that this change in accounting principle is
preferable. Based on our reading of management's stated reasons and
justification for this change in accounting principle in the Form 10-Q, and our
discussions with management as to their judgment about the relevant business
planning factors relating to the change, we concur with management that such a
change represents, in the Company's circumstances, the adoption of a preferable
accounting principle in conformity with Accounting Principles Board Opinion
No. 20.

We have not audited any financial statements of the Company as of any date or
for any period subsequent to December 31, 2000. Accordingly, our comments are
subject to change upon completion of an audit of the financial statements
covering the period of the accounting change.

Very truly yours,

/s/ PricewaterhouseCoopers LLP