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Abstract Background Prostate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics. Objective To compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC). Methodology We retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23. Results 114 patients were selected according to the inclusion criteria. Mean age was 68 years (61–75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant). Conclusion Hypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.