Background: The prevalence of hepatitis C virus (HCV) infection among thalassemic patients in Egypt ranged between 24 and 37%. Direct acting antivirals (DAAs) have revolutionized the standard of care for treatment of hepatitis in hemoglobinopathies. Objective: The aim of this study was to evaluate the safety, efficacy, and tolerability of ribavirin (RBV) free DAAs in thalassemic patients and its effect on transfusion requirements. Patients and Methods: In this study, 200 adult chronic hepatitis C (CHC) patients were enrolled. They were further divided into two groups. Group (I) included 150 HCV-thalassemic patients and group (II) included 50 HCV only patients. Sustained virological response (SVR) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for HCV-RNA 12 weeks post-treatment. Any treatment related adverse events were reported. Results: SVR was achieved in 89.33% in group (I) and in 92% in group (II). Among group (I), there was significant improvement in mean hemoglobin level after treatment. Moreover, mean ALT, AST, total and indirect bilirubin levels dropped significantly after treatment (P<0.001). There was decrease in blood transfusion requirements after treatment. There was no need to change or modify the dose of iron chelating agents. Apart from four patients in group (Ib) who developed hepatic fulmination and hepatocellular carcinoma requiring cessation of treatment, minor side effects were reported that were managed conservatively. Conclusion: RBV-free-DAAs are effective and well tolerated among HCV-thalassemic patients.