Backgroundand study aims:Hepatitis C virus (HCV) is the main leading cause of liver disease in Egypt. A new era of HCV treatment has been started with the evolution of direct acting antiviral agents. Sofosbuvir (SOF)-based therapy was introduced by the Egyptian ministry of health in 2014 in an attempt to decrease disease burden. We aimed to evaluate efficacy and safety of Sofosbuvir-based regimens in HCV Egyptian patients with compensated liver disease. Patients andMethod:This study was conducted in National Liver Institute, MenoufiaUniversity, Egypt. Seven hundred patients out of seven hundred fifty-eight chronic HCV patients with compensated liver disease who met the inclusion criteria were included. According to treatment regimen patients were divided to 4 groups; group 1 received Sofosbuvir (SOF), Pegylated interferon (PEG-IFN) plus ribavirin (RBV), group 2 received SOF plus RBV, group 3 received SOF and Simeprevir± RBV, group 4 received SOF and Daclatasvir ±RBV. Results:The overall SVR was 90.9%, 81.5%, 95% and 98% in groups 1, 2, 3, and 4 respectively. SVR in patients with liver cirrhosis was 90.56, 79.16, 95 and 96% in the 4 groups respectively. In treatment experienced patients, SVR was 86.8% in group 1, 78.3% in group 2, 100% in group 3 and 86.7% in group 4. Conclusion: Sofosbuvir plus daclatasvir with or without ribavirin is the safest andmost effective SOF-based regimen in treatment of HCV Egyptian patients with compensated liver disease.