Abstract: Purpose: To compare a conventional fractionation regimen with a hypofractionated regimen in the treatment of Epidemic Kaposi sarcoma with radiation therapy.Materials and methods: Sixty patients were randomized to receive a standard regimen of 24Gy in 12 fractions (ARM A) or the study regimen of 20Gy in five fractions (ARM B). Radiation technique was individualized. Treatment response, local control and toxicity were recorded.Results: Thirty five sites were treated in ARM A and 30 sites in ARM B. Treatment arms were similar for gender, ECOG performance score, treated site, antiretroviral therapy usage, T stage, I stage and S stage. The overall survival using the Kaplan Meier method was 37% at 1 year. Complete responses were recorded at 28 sites (13 Arm A,15 Arm B), partial responses at 19 sites (8 Arm A,11 Arm B) and stable disease at three sites (2 Arm A,1 Arm B). The mean time to maximum objective response was 3 months (range: 1–14 months). Response rates and local control were equal in the two arms (p=0.73 and 0.77, respectively, log rank test). Acute skin toxicity (p=0.77) and late skin toxicity (p=0.24) were equal in the two arms.Conclusion: The two treatment regimens produced equivalent results for treatment response, local recurrence-free survival and toxicity.