Abstract Background and aim As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world’s highest prevalence of Hepatitis C virus (HCV). The current study was designed to describe the efficacy and safety of Sofosbuvir plus Daclatasvir with or without Ribavirin in treatment of chronic HCV in a cohort of Egyptian patients who were referred to the viral hepatitis unit in El -Fayoum general hospital. Methods This is a prospective descriptive cross sectional study that describes the effect of 12 weeks of daily Sofosbuvir (SOF) 400 mg plus Daclatasvir (DCV) 60 mg with or without ribavirin (RBV) with dose adjustment if indicated. It included 200 patients that fulfilled the inclusion and exclusion criteria and treated in El -Fayoum general hospital, El-Fayoum, Egypt. Results In the current study, concerning viral response, SVR12 rate was achieved by 92.5% in the overall patients (185/200); by 98% (98/100) in group I, and by 87% (87/100) in group II. Concerning safety and tolerability, The main adverse effects recorded during and after 12 weeks of treatments were fatigue (46%), (66%); headache (24%), (40%); gastrointestinal upset (15%), (43%); and nausea (10%), (15%) in group 1 and group 2, respectively. Only one female patient in group II developed HCC. All patients completed treatment till the end of course. Conclusion The current study suggested that treatment of SOF plus DCV with/without RBV for chronic HCV patients in Egypt was generally safe, well tolerated, and of high efficacy, reflecting the antiviral potency and high resistance barrier of the combination regimen.