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Bckground: Adjuvant radiation therapy is commonly administered following breast-conserving surgery for breast cancer patients. Hypofractionated radiotherapy can significantly reduce the waiting time for radiotherapy, working load on machines, patient visits to radiotherapy departments and medical costs. Material/Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0) who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy in two arms (hypofractionated radiotherapy arm with 30 patients, dose 42.5 Gy in 16 fractions; and conventional radiotherapy arm with 22 patients, dose 50 Gy in 25 fractions). W compared these two groups in terms of overall survival, locoregional control, late skin complications and cosmetic results. Results: At a median follow-up of 52.4 months (range: 0–64 months), the follow-up rate was 82.6%. Overall, after 60 months, there was no detectable significant differences between groups regarding cosmetic results (p = 0.857), locoregional control or survival. Conclusions: The results confirm that hypofractionated radiotherapy with a subsequent boost is as effective as conventional radiotherapy, is well-tolerated and can be used as an alternative treatment method following breast conservation surgery., (Creative Commons Attribution License)