Introduction: The objective of this study was to evaluate the cost-effectiveness of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin in the treatment of chronic hepatitis C in HIV-HCV co-infection. Methods: We used a pre-existent Markov model of disease progression in which two cohorts of patients received peginterferon α-2a plus ribavirin or peginterferon α-2b plus ribavirin for 48 weeks and were followed for their expected lifetimes. The reference patient was a 40-year-old man or woman. The sustained virological response (SVR) with peginterferon α-2a plus ribavirin and peginterferon α-2b plus ribavirin, were taken from two different publications. Utilities and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs in 2005 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was conducted from the perspective of the Italian National Health Service. Results: For the two cohorts, expected life-years with peginterferon α-2a plus ribavirin versus peginterferon α-2a plus ribavirin were respectively 24.47 and 23.71 years. Quality-adjusted life years for peginterferon α-2a plus ribavirin were 12.93, and 12.49 for peginterferon α-2b plus ribavirin. The expected cost was € 19,858 with peginterferon α-2a plus ribavirin and €19,983 with peginterferon α-2b plus ribavirin. Conclusion: This economic evaluation suggests that peginterferon α-2a plus ribavirin is a dominant strategy versus peginterferon α-2b plus ribavirin for treatment of adults with HIV-HCV co-infection, under some assumptions regarding treatment effectiveness and model structure.