We aimed to investigate the efficacy and safety of combination of sofosbuvir with ombitasvir, paritaprevir, and ritonavir ± ribavirin as a retreatment option for experienced Egyptian patients who failed previous sofosbuvir, daclatasvir ± ribavirin therapy. A total of 75 treatment-experienced patients were allocated for the completion of their treatment period according to criteria formed by the national committee for control of viral hepatitis. The enrolled patients were followed up throughout treatment, at the end of treatment and 3 months after the end of the treatment by clinical evaluation and laboratory investigations. 27 patients were treated with sofosbuvir with ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12 weeks while 48 patients were treated with sofosbuvir with ombitasvir, paritaprevir, and ritonavir without ribavirin for 24 weeks. The per-protocol sustained virological response at week 12 (SVR12) rate was 100% in both groups while the intentionto-treat SVR12 was 93.4% in all patients, 97.9% in the 24 weeks group and 85.2% in the 12 weeks group. The regimen was well tolerated and the most common adverse effects observed across treatment and during follow-up period included fatigue (38.6%) and headache (29.3%), withdrawal due to adverse effects occurred in 6.6%. We can conclude that retreatment with sofosbuvir with ombitasvir, paritaprevir, and ritonavir ± ribavirin is well tolerated and achieved high SVR12 rates in chronic HCV Egyptian patients with previous sofosbuvir plus daclatasvir treatment failure. Ribavirin free regimen for 24 weeks exerted significant lesser adverse effects.