BACKGROUND: Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy. METHODS: We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages. RESULTS: The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with > or =85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = .04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with > or =85% adherence (3.32 vs. 2.32 log IU/mL; P = .01). Early virologic response was more common among patients with > or =85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = .02) and ribavirin (73% vs. 55%; P = .08). CONCLUSIONS: Adherence of > or =85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with > or =85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage.