The treatment of chronic hepatitis C (CHC) with peginterferon alpha-2b/ribavirin (PegIFN + Rib) produced larger sustained viral response (SVR) compared to the conventional (non-pegylated) interferon/ribavirin (IFN + Rib), but its cost-effectiveness was not assessed in Brazil. We developed a Markov model to mirror the natural disease history and cohorts of patients with hepatitis C virus (HCV), that received PegIFN + Rib or IFN + Rib treatment for 48 or 24 weeks, according to viral genotype and liver histology. The SVRs for the treatments PegIFN + Rib and IFN + Rib were respectively 48% and 34% (genotype 1), and 88% and 80% (genotype non-1). Three Delphi panels were conducted with hepatologists and intensivists, and another one with oncologists. The costs are expressed in 2006 Brazilian Reais (R$) and the benefits were discounted at 3%. In genotype 1 HCV patients, PegIFN + Rib increases the life expectancy (LE) in 0.51 year, and the quality-adjusted life years (QALY) in 0.78, as compared to IFN + Rib. In genotype non-1 HCV patients, PegIFN + Rib increases the LE in 0.29 years and the QALY in 0.44 years, as compared to IFN + Rib. The incremental cost-effectiveness rate, considering all the genotypes, was of R$19,848.34 per QALY. Peginterferon alpha-2b with ribavirin is a cost-effective therapy for the treatment of naïve CHC adult patients compared to the interferon alpha-2b and ribavirin regime, irrespective of the viral genotype.