This article reports the results of two phase 3 clinical trials evaluating the efficacy and safety of sofosbuvir in the treatment of chronic hepatitis C (HCV) infection in previously untreated patients. The first trial, NEUTRINO, involved 327 patients with HCV genotypes 1, 4, 5, or 6, who received sofosbuvir, peginterferon alfa-2a, and ribavirin for 12 weeks. A sustained virologic response (SVR) was achieved in 90% of patients. The second trial, FISSION, involved 499 patients with HCV genotypes 2 or 3, who were randomly assigned to receive either sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. SVR was achieved in 67% of patients in both groups. Sofosbuvir demonstrated high efficacy across all HCV genotypes, with SVR rates of 90% in the NEUTRINO trial and 67% in the FISSION trial. Response rates were lower in patients with genotype 3 infection compared to those with genotype 2 infection. Adverse events were less common with sofosbuvir than with peginterferon. The study found that sofosbuvir was noninferior to peginterferon in the treatment of HCV genotypes 2 and 3. The study also found that sofosbuvir had a high genetic barrier to resistance, with no resistance-associated mutations detected in patients. The results suggest that sofosbuvir is a promising treatment option for HCV infection, particularly for patients with genotypes 1 and 4, and for those with genotypes 2 and 3. The study was funded by Gilead Sciences and was conducted in collaboration with multiple institutions. The findings support the use of sofosbuvir in combination with ribavirin for the treatment of HCV infection.This article reports the results of two phase 3 clinical trials evaluating the efficacy and safety of sofosbuvir in the treatment of chronic hepatitis C (HCV) infection in previously untreated patients. The first trial, NEUTRINO, involved 327 patients with HCV genotypes 1, 4, 5, or 6, who received sofosbuvir, peginterferon alfa-2a, and ribavirin for 12 weeks. A sustained virologic response (SVR) was achieved in 90% of patients. The second trial, FISSION, involved 499 patients with HCV genotypes 2 or 3, who were randomly assigned to receive either sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. SVR was achieved in 67% of patients in both groups. Sofosbuvir demonstrated high efficacy across all HCV genotypes, with SVR rates of 90% in the NEUTRINO trial and 67% in the FISSION trial. Response rates were lower in patients with genotype 3 infection compared to those with genotype 2 infection. Adverse events were less common with sofosbuvir than with peginterferon. The study found that sofosbuvir was noninferior to peginterferon in the treatment of HCV genotypes 2 and 3. The study also found that sofosbuvir had a high genetic barrier to resistance, with no resistance-associated mutations detected in patients. The results suggest that sofosbuvir is a promising treatment option for HCV infection, particularly for patients with genotypes 1 and 4, and for those with genotypes 2 and 3. The study was funded by Gilead Sciences and was conducted in collaboration with multiple institutions. The findings support the use of sofosbuvir in combination with ribavirin for the treatment of HCV infection.