BACKGROUND: To evaluate efficacy and morbidity prospectively in a contemporary multi-institutional salvage radical prostatectomy (SRP) series. METHODS: Forty-one men were enrolled between 1997 and 2006, who suffered biopsy-proven recurrent prostate cancer (CaP) after receiving > /= 60c Gy radiation as primary treatment for cT1-2NXM0 disease. Surgical morbidity, quality of life, biochemical progression-free survival (BPFS) and overall survival (OS) were evaluated. RESULTS: Twenty-four men had undergone external beam radiotherapy, 11 brachytherapy, and six both. Median time between radiation and SRP was 64 months. Median age at SRP was 64 years. Pathologic staging revealed 44% pT2, 54% pT3, and 3% pT4. Surgical margins were positive in 17 and 88% were pN0. Twenty-two percent required intraoperative blood transfusion. Three rectal and one obturator nerve injuries occurred. Seventeen of 38 evaluable patients (45%) had urinary incontinence ( > /= 3 pads/day) prior to SRP; 88% reported urinary incontinence at 6 months, 85% at 12 months, 63% at 24 months after SRP. Furthermore, 37% of men reported impotence prior to SRP; 78% reported impotence at 6 months, 82% at 12 months, and 44% at 24 months after SRP. The 2-, 5- and 10-year BPFS rates were 51, 39, and 33% respectively; the 2-, 5- and 10-year OS rates were 100, 89, and 52%, respectively, at median follow-up 91 months. CONCLUSIONS: Modern surgical techniques continue to be associated with significant peri-operative complication rates. Nevertheless, SRP may benefit carefully selected patients through durable oncologic control.