ABSTRACT: Prevalence of chronic hepatitis C virus (HCV) infection is high among incarcerated persons in the United States. New, short-duration, high-efficacy therapies may expand treatment eligibility in this population.To assess the cost-effectiveness of sofosbuvir for HCV treatment in incarcerated populations.Markov model.Published literature and expert opinion.Treatment-naive men with chronic, genotype 1 HCV monoinfection.Lifetime.Societal.No treatment, 2-drug therapy (pegylated interferon and ribavirin), or 3-drug therapy with either boceprevir or sofosbuvir. For inmates with short remaining sentences (<1.5 years), only no treatment or sofosbuvir 3-drug therapy was feasible; for those with long sentences (?1.5 years; mean, 10 years), all strategies were considered. After release, eligible persons could receive sofosbuvir 3-drug therapy.Discounted costs (in 2013 U.S. dollars), discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.The strategies yielded 13.12, 13.57, 14.43, and 15.18 QALYs, respectively, for persons with long sentences. Sofosbuvir produced the largest absolute reductions in decompensated cirrhosis (16%) and hepatocellular carcinoma (9%), resulting in 2.1 additional QALYs at an added cost exceeding $54,000 compared with no treatment. For persons with short sentences, sofosbuvir cost $25,700 per QALY gained compared with no treatment; for those with long sentences, it dominated other treatments, costing $28,800 per QALY gained compared with no treatment.High reinfection rates in prison attenuated cost-effectiveness for persons with long sentences.Data on sofosbuvir's long-term effectiveness and price are limited. The analysis did not consider women, Hispanic persons, or patients co-infected with HIV or hepatitis B virus.Sofosbuvir-based treatment is cost-effective for incarcerated persons, but affordability is an important consideration.National Institutes of Health.