The aim of this cross-sectional study was to compare single with repeated high-intensity focused ultrasound (HIFU) treatment in patients with localized prostate cancer, regarding treatment-related morbidity. A number of 223 consecutive patients with localized prostate cancer were treated with HIFU. Among them, 174 (78%) patients had one treatment, while 49 (22%) needed a second treatment. The patients' status and treatment-related side effects were followed up. The complications rates after one HIFU in 223 patients were: urinary tract infection 0.4%, chronic pelvic pain 0.9%, infravesical obstruction 19.7%, stressincontinence 7.6%, impotence 49.8%. Among the 49 patients who received a second HIFU therapy, the cumulative incontinence rate (12.2%; P = 0.024) and cumulative impotence rate (55%; P < 0.001) were significantly increased. Although there is an increase in morbidity if transrectal HIFU is repeated, the risk of side effects related to additional HIFU sessions in the case of primary treatment failure is still low.