PURPOSE: High intensity focused ultrasound for the treatment of primary prostate cancer is increasing in a subset of men seeking definitive treatment with reduced morbidity. We review outcomes in men undergoing salvage radical prostatectomy after failed whole gland high intensity focused ultrasound. MATERIALS AND METHODS: Prospective data were collected for men presenting with an increasing prostate specific antigen and biopsy proven prostate cancer after high intensity focused ultrasound from 2007 to 2010 who underwent salvage open radical prostatectomy with a 22-month median followup, including prostate specific antigen, prostate volume, pathology results, continence and erectile function. RESULTS: Data for 15 men were available, including median age 64 years (IQR 55-69), Gleason score before high intensity focused ultrasound of 6 (8), Gleason score 7 (7), median cores positive 39% (IQR 17%-63%) and median prostate specific antigen 7 ng/ml (IQR 5-8). Whole gland high intensity focused ultrasound achieved median nadir prostate specific antigen 1.1 ng/ml (IQR 0.5-3.1). Biopsy after high intensity focused ultrasound demonstrated Gleason score 6 (in 3 patients), 7 (9) and 8/9 (3), and 42% (IQR 25%-50%) cores positive and a median time from high intensity focused ultrasound to radical prostatectomy of 22 months (IQR 7-26). Perioperative morbidity was limited to 1 transfusion in a patient with a rectal injury. Pathologically extensive periprostatic fibrosis was found with persistent prostate cancer, as pT3 disease (in 9 of 14), Gleason scores 6 (2), 7 (9) and 8 of 9 (4), with focally positive margins in 3 of 11 (pT3a). Postoperative prostate specific antigen was unrecordable in 14 of 15 patients with further treatment in 2. Postoperative continence (more than 12 months of followup) yielded no pad use in 6 of 10 men with universally poor erectile function. CONCLUSIONS: Radical prostatectomy as salvage is feasible for men in whom high intensity focused ultrasound failed, but with a higher morbidity than for primary surgery. Pathology results are alarming given the number of cases with extraprostatic extension yet early followup data suggest acceptable oncologic control. These results should be factored in when counseling men who wish to undergo primary high intensity focused ultrasound.