OBJECTIVES: To assess cost-effectiveness of pegylated interferon alpha-2a (PegIFNα2a) vs. pegylated interferon alpha-2b (PegIFNα2b) in the treatment of chronic hepatitis C (HCV) patients from Polish public payer perspective. METHODS: Systematic review assessed clinical efficacy and safety of the two treatment options. Seven state Markov model (chronic HCV, sustained virological response, compensated cirrhosis, hepatocellulare carcinoma, liver transplantation and death) was used to estimate clinical effects and costs in lifetime horizon, from Polish public payer perspective. Direct medical costs were considered. Separate analysis was done for genotypes 1,4 (48-week treatment) and genotypes 2,3 (24-week treatment). Clinical practice and cost data were gathered from clinical experts or based on the National Health Fund and Ministry of Health published price lists. Sensitivity analysis was conducted in order to assess the robustness of the results. RESULTS: Genotypes 1 and 4: total costs were 92 036 PLN (1 Euro=3.96 PLN) for PegIFNα2a and 87 793 PLN for PegIFNα2b.  Average survival of HCV patient treated with PegIFNα2a was 27.9 life years (LY) and 14.83 quality adjusted life years (QALY) and treated with PegIFNα2b was 27.63 LYs and 14.61 QALYs. The incremental cost-effectiveness ratio was 15 878 PLN/LYG and incremental cost-utility ratio was 19 763 PLN/QALY. Values of both ratios fall below the cost-effectiveness threshold assumed in Poland (100 000 PLN/LYG or QALY). Genotypes 2 and 3: Total costs were 32 849 PLN for PegIFNα2a and 38 071 PLN for PegIFNα2b.  Average survival of HCV patient treated with PegIFNα2a was 30.79 LYs and 17.15 QALYs and treated with PegIFNα2b was 30.20 LYs and 16.68 QALYs. The PegIFNα2a dominated PegIFNα2b. The results were confirmed in sensitivity analysis. CONCLUSIONS: PegIFNα2a is a clinically effective and safe treatment for HCV patients and is highly cost-effective (or dominant) from Polish public payer perspective.