OBJECTIVES: To report on the long-term results of high-intensity focused ultrasonography (HIFU) in the treatment of localized prostate cancer. METHODS: Patients with clinical Stage T1-T2N0M0, biopsy-proven, localized prostate cancer, with a serum prostate-specific antigen (PSA) level of <or=20 ng/mL, Gleason score of <or=7, and with no previous curative prostate cancer treatment, were included. All patients underwent HIFU using the Ablatherm device and were required to have a minimal follow-up of 3 years after the last HIFU session to be included in this analysis. Follow-up included PSA measurement and biopsy performed 3-6 months after treatment and in conjunction with an increasing PSA level. Biochemical failure was defined according to the Phoenix definition (PSA nadir + 2 ng/mL). In determining the disease-free survival rate, treatment was considered to have failed if any of the following occurred: biochemical failure, positive biopsy findings, or the initiation of salvage treatment. RESULTS: The study included 163 patients. Within the 4.8 +/- 1.2 years of follow-up, no patient died of prostate cancer. Of the 163 patients, 86.4% achieved a PSA nadir of <1 ng/mL and 92.7% had negative post-treatment biopsy findings. The actuarial biochemical survival rate at 5 years was 75%. The actuarial disease-free survival rate at 5 years was 66%, with salvage treatment initiated for 12% of the patients. On multivariate analysis, the pretreatment PSA level was the only statistically significant predictive factor of recurrence (P = .005). CONCLUSIONS: The results after long-term follow-up have indicated that HIFU is an efficient and safe treatment for patients with localized prostate cancer.