Background: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and associated with an accelerated disease course. Second-generation direct-acting antivirals dramatically improve viral clearance. Their use in the Egyptian population in the post-transplant setting needs further evaluation. Objectives: To evaluate the safety and efficacy of sofosbuvir-based regimens in the treatment of HCV recurrence after LT in the Egyptian population. Patients and methods: Sixty patients with HCV recurrence after LT were included. Twenty patients received sofosbuvir (SOF) in combination with ribavirin (RBV) for 24 weeks, 21 patients received SOF and simeprevir (SIM) for 12 weeks and 19 patients received SOF and daclatasvir (DCV) with or without RBV for 12 or 24 weeks according to the stage of liver fibrosis and eligibility for ribavirin. Treatment response and adverse events were analyzed. Results: The mean age was 52.5±7.9 years. Most of patients were males (91.7%). Sustained virological response at week 12 after treatment (SVR12) was achieved in all patients who received SIM/SOF and SOF/DCV±RBV regimens and in 85% of patients who received SOF/RBV regimen. The most common reported adverse events were fatigue, anemia and hyperbilirubinemia. Fatigue was reported in 75% of patients in SOF/RBV group and in 85.7% of patients in SIM/SOF group. Anemia was reported in 15, 4.8 and 10.5% of patients in SOF/RBV, SIM/SOF and SOF/DCV±RBV groups respectively, whereas hyperbilirubinemia was documented in 10% of patients in SOF/SIM group and in 9.5% of patients in SIM/SOF group. Conclusion: Sofosbuvir-based combinations are safe and effective in the treatment of recurrent HCV after LT, especially when combined with another directly acting antiviral.