OBJECTIVES: Sofosbuvir (SOF) is a nucleotide polymerase inhibitor with excellent clinical efficacy in combination with ribavirin (RBV) for 12 weeks for patients who are chronically infected with hepatitis C virus (HCV) genotype 2.  A decision-analytic Markov model evaluated the health outcomes of SOF+RBV compared with current treatment options for patients who are previously untreated, had no response to prior interferon treatment, or are unable to take interferon. METHODS: The analysis modeled 3 cohorts of chronic HCV genotype 2 patients with an average age of 50 and 25% with cirrhosis at the start of treatment followed-up to 100 years of age from a US third-party payer perspective.  SOF+RBV for 12 weeks was compared with (1) pegylated interferon (PegIFN)+RBV for 24 weeks in the treatment-naïve patients, (2) PegIFN+RBV for 48 weeks in the treatment-experienced, and (3) no treatment in those unable to take interferon. Sustained virologic response (SVR) and adverse event rates were based on phase III clinical trials. Transition probability, utility, and cost estimates (in 2013 US dollars) were based on a literature review, public sources, and consensus by a panel of 4 hepatologists. RESULTS: In the treatment-naïve cohort, the SOF+RBV regimen resulted in an 83% decrease in the cases of liver disease complications including hepatocellular carcinoma, decompensated cirrhosis, liver transplant, and HCV-related death compared with PegIFN+RBV.  The reduction of the listed liver disease sequelae was 59% in the treatment-experienced vs. PegIFN+RBV and 93% in the interferon-unable cohort vs. no treatment.   The number needed to treat (NNT) with SOF+RBV rather than PegIFN+RBV to achieve one additional SVR was 6 in the treatment-naïve and 4 in the treatment-experienced cohorts.  CONCLUSIONS: SOF+RBV was projected to yield better health outcomes in genotype 2 patients compared to PegIFN+RBV, largely driven by superior efficacy, and the potential to cure those who are unable to take interferon-based therapies.