OBJECTIVES:  Telaprevir is a new direct acting antiviral for the treatment of G1 hepatitis C virus (HCV) infection. A post-hoc analysis was conducted to evaluate the cost-effectiveness of patients according to IL-28B subgroups in both treatment naïve and previously treated G1 chronic HCV patients. Cost-effectiveness is considered in terms of incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Wales. METHODS:  Two Markov-models were developed to evaluate treatments studied in TVR phase III clinical trials: TVR response-guided therapy of 12 weeks of TVR with PR [24 weeks PR for patients achieving an extended rapid viral response (eRVR), 48 weeks of PR for patients not achieving an eRVR] for treatment-naïve patients; 12 weeks of TVR in combination with 48 weeks of PR therapy for treatment-experienced patients. IL-28B data was available for 140 and 161 T12/PR and PBO/PR patients, equating to 39% and 45% of all T12/PR and PBO/PR patients in ADVANCE, respectively. IL-28B genotype data was available for 212 and 105 T12/PR and PBO/PR patients, equating to 80% of all patients in both treatment arms in REALIZE. Among T12/PR patients the CC, CT and TT distribution was 19%, 63% and 17% respectively; among PBO/PR patients the distribution was 16%, 55% and 29% respectively.  RESULTS: TVR based therapy was cost-effective when compared to PBO/PR regimen in both treatment-naïve and experienced patients regardless of IL-28B subtypes (CC, CT, and TT). CONCLUSIONS: The introduction of telaprevir to current standard of care for HCV genotype 1 patients is clinically more efficacious than PR alone and cost-effective at the £20,000 and £30,000 willingness-to-pay thresholds for both treatment-naïve patients and treatment-experienced patients regardless of IL-28B subtypes.