<p><b>Objective:</b> Across Japan, around 2 million people are infected with hepatitis C virus (HCV) with long-term complications such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplant (LT). Current treatment options have several limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological responses (SVR) rates, especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide analog NS5B polymerase inhibitor with pan-genotypic activity. SOF, administered in combination with ribavirin (RBV) with or without pegylated interferon (PEGIFN) resulted in high SVR rates across genotype (GT) 1–6 patients. It is also the first available regimen for patients that are unsuitable for interferon. This analysis assessed the cost–utility ratio of sofosbuvir in GT2 patients in Japan.</p> <p><b>Research design and methods:</b> A Markov model followed a cohort of 10,000 GT2 patients until patients reached 100 years of age. Approximately 20% of patients initiated treatment at the cirrhotic stage. Comparators were based on the current recommendations in Japan, including PEGIFN with ribavirin (RBV), telaprevir (TVR) in combination with PEGIFN + RBV and no treatment. Costs and outcomes were discounted at 2%.</p> <p><b>Results:</b> Sofosbuvir was cost-effective across all the studied indications, especially in patients unsuitable for interferon, with incremental cost–effectiveness ratios (ICERs) lower than JPY 5,000,000. Compared to the other treatments included in the analysis, SOF + RBV resulted in improved clinical outcomes. Results were robust to sensitivity analyses.</p> <p><b>Conclusion:</b> SOF combined with RBV was shown to be cost-effective in GT2 patients in Japan. Compared to PEGIFN + RBV, TVR + PEGIFN + RBV and no treatment SOF offers a more efficacious, shorter and better tolerated treatment option and extends treatment to reach HCV-infected patients who are ineligible for interferon-based regimens. Although adverse events were not included in the analyses, this would not make any changes to our conclusion.</p