Simple SummaryRecently, it has been shown that radiation therapy (RT) together with androgen-depletion therapy (ADT) might be more beneficial compared with ADT alone for clinically node-positive (cN1) prostate cancer. However, there are a limited number of studies that have addressed specific RT techniques and analyzed their clinical results. The present study was a retrospective analysis of cN1 prostate cancer patients treated with intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT), in addition to ADT, in our hospital. The present study suggests that ADT plus SIB-IMRT for cN1 prostate cancer treatment was safe and effective, was well tolerated, and had acceptable rates of late toxicity. Further prospective multicenter studies would be required to confirm the robustness of the present results.This study aimed to evaluate clinical outcomes and the toxicity of intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) combined with androgen-deprivation therapy for clinically node-positive (cN1) prostate cancer. We retrospectively analyzed 97 patients with cN1 prostate cancer who received SIB-IMRT between June 2008 and October 2017 at our hospital. The prescribed dosages delivered to the prostate and seminal vesicle, elective node area, and residual lymph nodes were 69, 54, and 60 Gy in 30 fractions, respectively. Kaplan–Meier analysis was used to determine 5-year biochemical relapse-free survival (bRFS), relapse-free survival (RFS), overall survival (OS), and prostate cancer-specific survival (PCSS). Toxicity was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0. Over a median follow-up duration of 60 months, the 5-year bRFS, RFS, OS, and PCSS were 85.1%, 88.1%, 92.7% and 95.0%, respectively. Acute Grade 2 genito-urinary (GU) and gastro-intestinal (GI) toxicities were observed in 10.2% and 2.1%, respectively, with no grade ≥3 toxicities being detected. The cumulative incidence rates of 5-year Grade ≥2 late GU and GI toxicities were 4.7% and 7.4%, respectively, with no Grade 4 toxicities being detected. SIB-IMRT for cN1 prostate cancer demonstrated favorable 5-year outcomes with low incidences of toxicity.