Objectives:To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon alfa (2a and 2b) combined with ribavirin in previously untreated patients with moderate to severe chronic hepatitis C, compared with the current standard treatment, which is nonpegylated interferon alfa combined with ribavirin.Methods:Systematic review and economic evaluation. A sensitive search strategy was applied to several electronic bibliographic databases. Relevant studies were critically appraised and meta-analyzed. A hypothetical cohort of 1,000 patients entered a Markov model and were followed up for a more than 30-year period to predict natural history, duration spent in each health state, and treatment costs.Results:Two fully published Phase III randomized controlled trials were included. Methodological quality was generally good. Dual therapy with pegylated interferon was significantly more effective than nonpegylated dual therapy with a pooled sustained virological response rate (SVR) of 55 percent (95 percent confidence interval [CI], 52–58 percent) compared with 46 percent (95 percent CI, 43–49 percent). The pooled relative risk of remaining infected was 0.83 (95 percent CI, 0.76–0.91 percent). Genotype was the strongest predictor of outcome, with SVRs in patients with the more responsive genotypes 2 and 3 reaching up to 80 percent. The incremental cost per quality-adjusted life year (QALY) for pegylated dual therapy compared with nonpegylated dual therapy was £12,123. The cost per QALY remained under £30,000 for most patient subgroups and in sensitivity analyses.Conclusions:Pegylated interferon is clinically effective, represents good value for the money, and is a significant advance in the treatment of this insidious disease.