OBJECTIVES Prior to approval of telaprevir (TPV), the treatment for chronic hepatitis C virus (HCV) included peginterferon (P) weekly injections and ribavirin (R) orally twice daily.  In 2011, TPV was approved for coadministration with P+R during the first 12 weeks.  Though TPV improved viral clearance, it also increased the treatment complexity by 2 pills given 3 times a day. The impact of increased regimen complexity on adherence is not well understood.  This study compared treatment adherence over 24 weeks in HCV patients treated with TPV+PR compared to those on PR. METHODS Large US commercial and Medicaid health insurance claims databases were used to identify HCV patients initiating treatment with PR (pre-TPV [2007 to 2009]) or TPV+PR (post-TPV [2011 to 2013]).  The index date was the date of HCV treatment initiation.  Adherence was measured by medication possession ratio for all patients at 4 week intervals thru 24 weeks.  Regression analyses adjusted for age, sex, comorbidities, liver disease severity, and pill count prior to HCV treatment.   RESULTS The study included 7,601 and 1,487 treated HCV patients in the commercial and Medicaid databases.  Unadjusted and adjusted adherence was high for both cohorts throughout the study period (>88% for Medicaid and >82% for the commercial at 24 weeks).  Adherence was not significantly different between the PR and T+PR cohorts at any time point in the Medicaid patients (88.9% [TPV+PR] and 90.5% [PR] at 24 weeks).  Adherence was also similar between the cohorts in the commercial patients (82.7% [TPV+PR] and 83.2% [PR] at 24 weeks) but was statistically different at weeks 8 and 12, though not clinically meaningful.   Age was the only factor consistently associated with adherence.   CONCLUSIONS Among HCV patients, adherence rates were high and were similar between the cohorts, despite the higher daily pill count for patients on TPV+PR.