To decrease side effects observed after high-intensity focused ultrasound (HIFU) treatment for localized prostate cancer and to re-establish normal micturition in a patient population that often presents with concomitant prostate enlargement, the impact of a combined transurethral resection of the prostate (TURP) and HIFU has been evaluated. TURP and HIFU treatments were performed under the same spinal anesthesia. For the HIFU treatments, the Ablatherm device (EDAP SA, Lyon, France) was used. Selection criteria for HIFU treatment were localized prostate cancer, no previous treatment for prostate cancer, and prostate-specific antigen (PSA) ≤ 15 ng/mL at diagnosis. All patients meeting these criteria were considered for treatment and analysis. PSA nadir and stability, histology, International Prostate Specific Score (IPSS) and IPSS-quality of life, and morbidity were assessed during follow-up; 271 patients were selected: 96 in the HIFU group and 175 in the TURP plus HIFU group. A statistically significant impact was observed on catheter time (40.0 days versus 7.0 in median), incontinence (15.4% versus 6.9%), urinary infection (47.9% versus 11.4%), and the evolution of the post-treatment IPSS (8.91 versus 3.37 in average) in favor of the TURP plus HIFU group. No significant changes were observed regarding efficacy during short-term follow-up when considering a 25% retreatment rate in the HIFU group versus a 4% retreatment rate in the TURP plus HIFU group. The combination of a TURP and HIFU treatment reduces the treatment-related morbidity significantly. The patient management after a combined TURP and HIFU treatment is comparable with the management after a single TURP.