Hepatitis C affects approximately 180 million people worldwide and is one of the main causes of chronic liver disease. HCV infection progresses to chronicity in approximately 80% of infected individuals, from whom up to 20% can develop cirrhosis over 20 years, thus  presenting high risk of complications related to hepatic insufficiency and/or hepatocellular carcinoma. OBJECTIVES: To compare treatment costs and outcomes of peginterferon-alfa-2a versus peginterferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks for hepatitis C genotype 2/3 in Brazilian Public Health System (SUS). METHODS: To project disease progression, a Markov model was built based on clinical stages of chronic disease.  A Delphi panel was conducted to evaluate direct medical resources related to each stage, followed by micro-costing of the results. Perspective was from a public payer. Source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs for a 70 kg patient were obtained from ’Banco de Preços em Saúde’, government official source. Costs were reported in 2009 Brazilian Reais (US$1≈$Brz1.7). Efficacy of pegylated-interferons was obtained from a meta-analysis of 7 RTCs comparing the drugs, detailed elsewhere. For genotype 2/3, median rate of sustained virological response was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. Discount rate for costs and outcomes was 5%, according to Brazilian guidelines for HTA. RESULTS: Assuming a lifetime perspective, expected costs and outcomes for peginterferon-alfa-2a were $Brz15,898, 15.21LYs and 14.57QALYs; for peginterferon-alfa-2b, $Brz18,439, 15.11LYs and 14.32QALYs. Cost-effectiveness analysis estimated an ICER of -$Brz25,289/LY and -$Brz10,426/QALYs for peginterferon-alfa-2a, being the dominant therapy. For each 1000 patients treated with peginterferon-alfa-2a instead of peginterferon-alfa-2b, savings granted can be up to $Brz2,5 million which would allow treatment of 160 more patients. CONCLUSIONS: These findings suggest that treatment with peginterferon-alfa-2a is more effective and less costly when compared to peginterferon-alfa-2b under SUS perspective in Brazil.