Background/Aim: The aim of the study was to evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity in patients with high- or intermediate-risk prostate cancer. Patients and Methods: We evaluated data of patients from three Radiation Oncology Departments (Rome, Lübeck and Perugia). Patients treated in Rome underwent exclusive intensity-modulated-radiotherapy (IMRT) or IMRT plus high-dose-rate interventional radiotherapy (HDR-IRT). IMRT plus two fractions HDR-IRT was performed in Lübeck, while in Perugia Helical Tomotherapy was performed. The Common Toxicity Criteria for Adverse Event (Version 4.03) scale was used to describe acute and late toxicity. Results: At a median follow-up of 28 months, all 51 patients were alive and disease-free. Patients treated by HDR-IRT plus VMAT showed only G1-2 genitourinary- gastrointestinal (GU-GI) acute and late toxicity. Univariate analysis showed a lower risk of acute GU toxicity (p=0.048) in IMRT+HDR-IRT. Conclusion: Low grade and less acute GU toxicity was observed in patients undergoing HDR-IRT boost.