Hepatitis C is caused by the hepatitis C virus. Various treatments for hepatitis C were ineffective before the use of direct-acting antivirals (DAAs). DAA has few (negative) adverse effects and high sustained virologic response rate (SVR12). The aim of this study was to investigate the efficacy and safety of (Velpatasvir-containing regimen) in adult chronic HCV patients unresponsive to Sofosbuvir plus Daclatasvir in Egypt. Patients were assessed clinically and laboratory at the baseline before beginning treatment regimen and monitored clinically and laboratory weekly in the follow up visits for 12 weeks, we report the adverse events t for the safety of the drug. At 12 weeks after treatment, RT-PCR was used to evaluate efficacy. A total of 102 patients. The average age was 55.64 ± 11.13 years old, with (87.3%) male and (12.7%) female. Most patients were treated with SOF+DAC for 3 months 72 (70.6%) while, 30 patients (29.4%) were treated with SOF+DAC+RBV for the same duration. SOF/VEL/VOX therapy had no adverse side effects. The SVR12 rate is 97%. In patients who failed Sofosbuvir plus daclatasvir combination therapy, this study found that combination therapies containing velpatasvir are effective and safe for treating HCV in Egypt.