Background: Hypofractionated regimen delivers greater than 2 Gy of radiation per fraction while reducing the total cumulative dose through reducing the number of treatment sessions. Radiobiologically, this approach appears to be as effective as the conventional schedule. Financially, this treatment method is useful in reducing breast cancer radiotherapy costs. Purpose: To evaluate the efficacy and toxicities of postmastectomy hypofractionated schedule compared to conventional fractionated radiotherapy. Methods: This study included one hundred and forty patients, they were randomly divided into two groups; Treatment group [hypofractionated radiotherapy group (N: 62)] received 40 Gy (2.67 Gy per fraction) over 3 weeks and Control group [conventional fractionated radiotherapy group (N: 78)] received 50 Gy (2 Gy per fraction) over 5 weeks, the radiation toxicities and local tumor control were compared in both groups. Results: The local recurrence and distant metastasis in hypofractionated group was 3.2% and 1.6% respectively while in conventional group were 3.8% and 2.6% respectively, grade II acute radiation dermatitis was reported in 22.6% in hypofractionated group versus 7.7% for patients receiving conventional radiotherapy, also, there was increase in the incidence of subcutaneous fibrosis in hypofractionated group in which grade II was reported in 17.7% versus 3.8% in conventional group, otherwise, other toxicities were comparable in both groups. Conclusion: Hypofractionated radiotherapy was tolerated and has comparable outcome compared to conventional fractionation regarding local tumor control and treatment toxicities.