OBJECTIVES: To assess the cost-effectiveness of simeprevir (SMV) plus peginterferon/ribavirin (PR) versus triple therapy regimens of boceprevir (BOC)/PR and telaprevir (TVR)/PR and PR dual therapy in treatment-naïve and treatment-experienced patients, chronically infected with hepatitis C virus (HCV) genotype 1, in Colombia. METHODS: A lifetime Markov model, applying a generally accepted structure, was used to estimate disease progression of HCV patients aged 50 years. Dosage regimens, including response-guided therapy were based on the approved labels for each product. Sustained viral response rates, were obtained from a mixed treatment comparison. Costs were estimated from health care system perspective and are expressed in local currency (COP). A review of the literature to obtain epidemiologic and resource utilization data was performed and when data were not available or validation was needed a Delphi panel with local experts was carried out. Primary outcomes included discounted quality adjusted life years (QALYs) and costs. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty. RESULTS: Treatment-naïve:  In comparison with TVR/PR, BOC/PR and PR, SMV/PR incurred 0.133, 0.171 and 0.858 additional QALYs, respectively. SMV/PR is dominant compared to BOC/PR and TVR/PR as more total QALYs are gained and less costs accrued. The cost-effectiveness ratio of SMV/PR vs. PR is estimated at COP 22,984,021/QALY. Treatment experienced: In comparison with TVR/PR, BOC/PR and PR, SMV/PR increased QALYs by 0.043, 0.133 and 1.064, respectively. SMV/PR is dominant compared to BOC/PR and TVR/PR as more total QALYs are gained and less costs accrued. The cost-effectiveness ratio of SMV/PR vs. PR is estimated at COP 22,437,019/QALY. These results were robust in the sensitivity analyses. CONCLUSIONS: SMV/PR dominated TVR/PR and BOC/PR, and is a cost-effective treatment option against WHO 3x GDP criteria in comparison to PR alone for treatment-naïve and treatment-experienced genotype 1 HCV patients in Colombia.