PURPOSE: To evaluate pre-operative prognostic risk factors to predict oncologic outcome of Salvage High-Intensity Focused Ultrasound (S-HIFU) for radiorecurrent prostate cancer (PCa). METHODS AND MATERIALS: A total of 290 men with biopsy-confirmed locally radiorecurrent PCa, underwent S-HIFU. D'Amico risk group before external beam radiotherapy (EBRT), Prostate Specific Antigen (PSA), estimated Gleason score prior HIFU and post HIFU biopsies were analyzed for predictive utility of local cancer control, cancer-specific, metastasis free, and progression free survival rates (PFSR). RESULTS: Local cancer control with negative biopsy results was obtained in 81% of the 208 patients who underwent post-S-HIFU biopsies. Median PSA nadir was 0.14 ng/ml and 127 patients did not require androgen deprivation therapy (ADT). The mean follow up was 48 months for cancer-specific survival rates. The cancer-specific and metastasis-free survival rates at 7 years were 80% and 79.6% respectively. The PFSR was significantly influenced by: the pre-HIFU PSA level (hazard ratio (HR): 1.09, 95% CI 1.04-1.13), a Gleason score ≥8 versus ≤6 (HR: 1.17, 95% CI 1.03-1.3), and a previous ADT (HR: 1.28, 95% CI 1.09-1.46). The rates of recto-urethral fistula (0.4%) and grade II/III incontinence (19.5%) indicate significant reduction in serious side effects with use of dedicated post-radiation acoustic parameters compared with standard parameters. CONCLUSION: S-HIFU is an effective curative option for radiorecurrent PCa with acceptable morbidity for localized radiorecurrent PCa, but should be initiated early following EBRT failure. Use of prognostic risk factors can optimize patient selection.