To compare tumour control and toxicity outcomes with the use of high-dose intensity-modulated radiation therapy (IMRT) alone or brachytherapy combined with IMRT (combo-RT) for patients with intermediate-risk prostate cancer. Between 1997 and 2010, 870 consecutive patients with intermediate-risk prostate cancer were treated at our institution with either 86.4 Gy of IMRT alone (n = 470) or combo-RT consisting of brachytherapy combined with 50.4 Gy of IMRT (n = 400). Brachytherapy consisted of low-dose-rate permanent interstitial implantation in 260 patients and high-dose-rate temporary implantation in 140 patients. The median (range) follow-up for the entire cohort was 5.3 (1-14) years. For IMRT alone vs combo-RT, 7-year actuarial prostate-specific antigen (PSA)-relapse-free survival (PSA-RFS) rates were 81.4 vs 92.0% (P < 0.001), and distant metastases-free survival (DMFS) rates were 93.0 vs 97.2% (P = 0.04), respectively. Multivariate analysis showed that combo-RT was associated with better PSA-RFS (hazard ratio [HR], 0.40 [95% confidence interval, 0.24-0.66], P < 0.001), and better DMFS (HR, 0.41 [0.18-0.92], P = 0.03). A higher incidence of acute genitourinary (GU) grade 2 (35.8 vs 18.9%; P < 0.01) and acute GU grade 3 (2.3 vs 0.4%; P = 0.03) toxicities occurred in the combo-RT group than in the IMRT-alone group. Most acute toxicity resolved. Late toxicity outcomes were similar between the treatment groups. The 7-year actuarial late toxicity rates for grade 2 gastrointestinal (GI) toxicity were 4.6 vs 4.1% (P = 0.89), for grade 3 GI toxicity 0.4 vs 1.4% (P = 0.36), for grade 2 GU toxicity 19.4 vs 21.2% (P = 0.14), and grade 3 GU toxicity 3.1 vs 1.4% (P = 0.74) for the IMRT vs the combo-RT group, respectively. Enhanced dose escalation using combo-RT was associated with superior PSA-RFS and DMFS outcomes for patients with intermediate-risk prostate cancer compared with high-dose IMRT alone at a dose of 86.4 Gy. While acute GU toxicities were more prevalent in the combo-RT group, the incidence of late GI and GU toxicities was similar between the treatment groups. © 2013 The Authors. BJU International © 2013 BJU International.