OBJECTIVES: Direct acting antiviral therapies (DAA) in addition to PEG 2a + RBV (PR) are a new therapeutic option with higher rates of sustained virological response (SVR) than dual therapy (PR) alone in chronic hepatitis C. Currently, two alternatives of DAA, telaprevir (TVR) and boceprevir (BOC), are available in Venezuela. The aim of this study was to evaluate the cost-effectiveness of adding TVR to PR in treatment naive and previously treated patients with HCV in Venezuela compared to PR alone and with the addition of BOC. METHODS: A lifetime Markov model was developed including HCV, cirrhosis, liver transplant and death as health states. QALYs as an outcome measure, a health care system perspective and a 5% discount rate for health benefits and costs have been used. Costs are expressed in local currency. A review of the literature to obtain epidemiologic and resources utilization data was performed and when data were not available or validation was needed a Delphi panel with local experts was carried out. Deterministic and probabilistic sensitivity analysis was performed. RESULTS: In comparison with PR, TVR avoided 174 cirrhosis cases and 20 deaths per 1,000 patients and shown an ICER of $70,149/QALY and $29,689/QALY for the naïve and for the previously treated patients respectively. TVR dominated BOC in naïve patients and in most of the previously treated ones (was less costly and more efficacious), except in the partial responders subgroup. These results were robust in the sensitivity analysis. CONCLUSIONS: TVR dominated BOC and was cost-effective against WHO 3GDP criteria in comparison to double therapy from the national healthcare system perspective in Venezuela.