OBJECTIVES: To assess the cost-effectiveness and cost-utility of simeprevir (SMV) plus peginterferon/ribavirin (PR) versus boceprevir (BOC)/PR in treatment-naïve patients [METAVIR F0-F3], versus PR in treatment-naïve [F0-F3 and F4] and treatment-experienced patients in partial and null responders [F0-F4], and versus “no treatment” in treatment-experienced patients [F0-F4], chronically infected with hepatitis C virus (HCV) genotype 1, in Mexico. METHODS: A lifetime Markov model, was used to estimate disease progression for treatment-naïve and treatment-experienced patients aged 47.8 years. Dosage regimens, including response-guided therapy and futility stopping rules, were based on Mexican HCV treatment guidelines. Sustained viral response rates were obtained from relevant phase II/III clinical trials. Patient baseline characteristics, mortality, discount rates and unit costs were obtained from local sources and an advisory board. HCV progression rates and health related quality of life estimates were based on published literature and HCV cost-effectiveness models.  Sensitivity analyses were conducted to estimate discounted quality adjusted life years (QALYs) and costs (in Mexican pesos). RESULTS: In the treatment-naïve, F0-F3 population, SMV/PR was the dominant alternative, accruing more QALYs and less costs per patient compared to BOC/PR and PR alone (11.25 vs 11.08 and 10.67; $348,355 vs $455,709 and $368,416, respectively). Likewise, SMV/PR was the dominant treatment option when compared with PR alone in the treatment-naïve, F4 population (7.43 vs 6.85 QALYs; $668,475 vs $731,854, respectively) and treatment-experienced (9.27 vs 8.42; $559,697 vs $609,751, respectively). Compared to “no treatment”, more costs and more QALYs were accumulated resulting in an incremental cost-utility ratio of $43,116 in the treatment-experienced population. Multivariate probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of $100,000, the probability that SMV/PR is cost-effective was >80% for all treatment groups. CONCLUSIONS: SMV/PR appears a cost-effective treatment option in genotype 1 HCV patients compared to other regimens currently available in Mexico, regardless of treatment experience and fibrosis.