OBJECTIVES: To investigate the cost-effectiveness of therapy of chronic hepatitis C with peginterferon alfa-2b and ribavirin in the context of the Slovak healthcare system. METHODS: We retrospectively obtained clinical data on the cost of treatment in 140 patients with chronic hepatitis C or advanced chronic liver disease of other etiology. Life-time cost of untreated and treated chronic hepatitis C was calculated using the Markov model and cost-effectiveness of antiviral therapy was evaluated by cost per life-year saved (LYS) analysis. RESULTS: The average medical cost per patient-year in case of chronic hepatitis C not treated with antiviral drugs, compensated cirrhosis, complicated cirrhosis, and after liver transplantation was 578 USD Sk (33,50 Slovak crowns=1 USD), 926 USD, 5890 USD, and 9997 USD, respectively. The cost per life-year saved using 3 % discounting was 3156 USD in the average group of patients and 5711 USD in patients with genotype 1. In patients with genotype 2 and 3 antiviral treatment would result in a life-time cost saving of 492 USD per patient. CONCLUSION: The cost of treatment of chronic hepatitis C and other chronic liver diseases in Slovakia is comparable with countries with more advanced economies. The treatment of chronic hepatitis C with peginterferon alfa-2b and ribavirin in Slovakia is cost-effective based on pharmacoeconomic calculations.