OBJECTIVES: Hepatitis C is a disease with significant economic burden to healthcare systems. Two recently approved protease inhibitors –telaprevir (TVR) and boceprevir (BOC)- are expected to change the current treatment algorithm, since their addition to peginterferon and ribavirin (PR) is associated with significantly improved clinical outcomes compared to PR alone. This analysis aims to evaluate the cost-effectiveness of a triple regimen with telaprevir (TVR+PR) compared to one with boceprevir (BOC+PR) from the Greek National Health Service perspective. METHODS: A decision analytic model based on treatment pathways and efficacy data from four phase III clinical trials (Advance, Sprint-2, Realize and Respond-2) was used to assess the cost-effectiveness of TVR+PR and BOC+PR . Clinical outcome was measured in terms of sustained virologic response (SVR) rates. Drug costs were estimated based on available EU prices in March 2012. We estimated the average cost per cured (SVR) patient and ICERs over treatment naïve and experienced patients and over the overall HCV G1 population (with a ratio of 1 to 4). Treatment stopping rules were not considered in this analysis. One way sensitivity analysis was performed over the proportion of naïve patients. Resource allocation implications were also considered under a hypothetical fixed budget scenario. RESULTS: The average cost per cured patient in the overall HCV G1 population was €46.635 for TVR+PR and €56.146 for BOC+PR. In treatment naïve patients it was €38.868 for TVR+PR and €42.983 for BOC+PR, whereas in treatment experienced patients it was €48.966 and €59.902 respectively. In terms of ICERs TVR+PR was associated with lower costs and higher SVR rates, with an ICER of - €10.403 per cured patient gained in the overall patient population. Results were robust in sensitivity analysis. CONCLUSIONS: TVR+PR was projected to be cost-effective compared to BOC+PR, allowing for more patients to be cured under a hypothetical fixed budget.