OBJECTIVES: To assess the cost-effectiveness of simeprevir plus sofosbuvir +/- ribavirin (SMV/SOF) versus sofosbuvir plus peginterferon/ribavirin (SOF/PR) and SOF/R regimens in treatment-naïve (METAVIR F3-F4) and prior-null-responder patients (F0-F4) infected with genotype 1 HCV in the Dominican Republic (DR). METHODS:  A Markov model, based on existing cost-effectiveness analyses, was applied to estimate disease progression of a cohort of genotype 1 HCV patients aged 47.8 years over a life time horizon. Sustained viral response (SVR) rates were obtained from the COSMOS study for SMV/SOF, from NEUTRINO for SOF/PR and from SPARE and QUANTUM for SOF/R. SVR rates for SOF/R and SOF/PR in null responder patients were conservatively assumed equal to treatment-naïve patients. Patient baseline characteristics, mortality, discount rates and unit costs were obtained from local sources. HCV progression rates and health related quality of life estimates were based on literature and HCV cost-effectiveness models. Various sensitivity and scenario analyses were conducted to assess uncertainty around the estimated discounted quality adjusted life years (QALYs) and costs. RESULTS: In the treatment-naïve patient population, SMV/SOF accrued 0.59 more QALYs and incurred $330,982 less costs per patient compared to SOF/R, resulting in SMV/SOF as the dominant treatment option. Compared to SOF/PR, SMV/SOF accrued 0.08 additional QALYs and $52,319 additional costs resulting in a cost-effectiveness ratio of $626,676 and was cost-effective against WHO 3GDP criteria. In the prior-null-responder population, SMV/SOF dominated both comparators. Multivariate probabilistic sensitivity analyses showed that at a willingness-to-pay of $1,000,000, the probability of SMV/SOF being cost-effective was estimated at 62% and 92% in the treatment-naïve and prior null responder population, respectively. CONCLUSIONS: SMV/SOF provides higher efficacy compared to its competitors, especially for patients that are more difficult to treat (prior null responders). Compared to SOF/R and SOF/PR, SMV/SOF represents a cost-effective treatment option to treat genotype 1 HCV patients in DM.