OBJECTIVE To evaluate the biochemical disease‐free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high‐intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. PATIENTS AND METHODS In all, 63 patients with stage T1c‐2bN0M0 localized prostate cancer underwent HIFU using the SonablateTM system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate‐specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow‐up were 71 (45–87)  years, 8.5 (3.39–57.0) ng/mL and 22.0 (3–63)  months, respectively. RESULTS The overall biochemical disease‐free rate was 75% (47 patients). The 3‐year biochemical DFS rates for patients with a PSA level before HIFU of <10, 10.01–20 and >20 ng/mL were 82%, 62% and 20% (P < 0.001), respectively. The 3‐year biochemical DFS rates for patients with a PSA nadir of <0.2, 0.21–1 and >1 ng/mL were 100%, 74% and 21% (P < 0.001), respectively. Final follow‐up sextant biopsies showed that 55 (87%) of the patients were cancer‐free. Multivariate analysis showed that the PSA nadir (P < 0.001) was a significant independent predictor of relapse. CONCLUSION HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.