Background:  High‐intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease‐free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. Methods:  A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate‐specific antigen (PSA) level were 70 years (range 44–88) and 9.76 ng/mL (range 3.39–89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow‐up period for all patients was 18.0 months (range 4–68). Results:  The biochemical disease‐free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease‐free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01–20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P < 0.0001). Multivariate analysis identified pretreatment PSA (P < 0.0001) as a independent predictor of relapse. Conclusion:  High‐intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.