Objective Postoperative radiotherapy (RT) is an established treatment for prostate cancer (PC). Though hypofractionation is commonly used for radical treatments, open issues still remain in the postoperative setting due to the lack of long-term data. Aim of this study was to evaluate long-term results of postoperative moderately hypofractionated RT (MHRT). Methods We conducted a retrospective analysis including PC patients treated with prostatectomy and postoperative MHRT delivered with volumetric modulated arc therapy (VMAT). Endpoints of the analysis included biochemical relapse-free survival (BRFS), distant metastases free-survival (DMFS), overall survival (OS), and pattern of acute and late toxicity. Results 181 patients were included. Pathological stage was classified as pT3a in 33.6% and pT3b in 30%. Median PSA value before RT was 0.23 ng/ml and median RT total dose was 70 Gy (65–74.2 Gy) in 25/28 fractions. With a median follow-up of 54.5 months, rates of BRFS at 3 and 5 years were 80.7 and 72.3%. ISUP grade group (HR 1.44, p  = 0.015), pathological T stage (HR 2.03; p  = 0.009), and pre-RT PSA >0.2 ng/ml (HR 2.64; p  = 0.015) were correlated with BRFS. Three and 5‑year DMFS were 87.4 and 80.8%. ISUP grade group (HR 1.50; p  = 0.011) and pre-RT PSA (HR 5.34; p  = 0.001) were correlated with DMFS. Five (2.7%) and 3 (1.6%) patients reported late grade 3 GU and GI toxicity, respectively. Conclusion Our results confirm the long-term safety and efficacy of postoperative MHRT for PC. Advances in knowledge The present paper demonstrates the long-term safety and efficacy of MHRT for postoperative prostate cancer. Reduction of treatment time in long-course radiotherapy has advantages in terms of both patients’ quality of life and departmental organization.