OBJECTIVES: Poor adherence to antiviral therapy in hepatitis C virus (HCV) patients is a well-documented problem. The Be In Charge® program (BIC) is a comprehensive patient support program that encourages adherence by providing 24-hour inbound and proactive outbound telephone nursing support and mailings of HCV educational materials throughout therapy. The purpose was to determine the impact of BIC on patient adherence to peginterferon alfa-2b combination therapy (peg-2b). METHODS: A retrospective cohort analysis compared BIC enrollees to propensity-score matched peg-2b starters not enrolled in BIC (controls). Subjects were included if they were =18 years of age; started peg-2b on or after January 1, 2004; and could be observed for at least 12 weeks after treatment initiation. Adherence was measured as the number of injections dispensed and proportion of patients who received an average of =1 injection per week during follow-up. Adherence was compared using paired chi-square and t-test. RESULTS: After matching, each cohort consisted of 780 eligible subjects observable for =12 weeks; 638 and 333 subjects in each cohort were observable for 24 and 48 weeks, respectively. BIC subjects refilled 1.2 more injections (95% confidence interval [CI] 0.52, 1.83; P<0.0001) than the control cohort within 12 weeks, 2.7 more (95% CI 1.5, 3.8; P<0.0001) within 24 weeks, and 6.7 more (95% CI 4.3, 9.1; P<0.0001) within 48 weeks. Additionally, BIC enrollees were more likely to refill =12 injections within 12 weeks of initiation (72% vs. 64%, P=0.0005), =24 injections within 24 weeks (52% vs. 41%, P<0.0001), and =48 injections within 48 weeks (22% vs. 13%, P=0.0020). CONCLUSION: This quasi-experimental study suggest the BIC program significantly improved adherence to peg-2b. Additional research is needed to ascertain which aspects of the program are most effective and which patients are most likely to benefit from this intervention.