Background: In the field of curative treatment for localized prostate cancer, HIFU (High Intensity Focused ultrasound) is one of salvage option after EBRT(external beam radiation therapy) failure and EBRT is the standard salvage option for local relapse after HIFU.Our aim was to compare and evaluate the oncologic outcomes between HIFU first + salvage EBRT versus EBRT first +salvage HIFU. Methods: Using a matched pair analysis, 342 Patients (171 in each group) treated between 1994 and 2014 in the same institution were prospectively followed and matched to a 1:1 basis. Outcome measurements: Overall Survival Rate(OSR), cancer specific(CSSR) and metastasis free (MFSR) survival rates were the primary endpoints. Secondary endpoints were survival rate free of hormone therapy (HTFR) and the rate of side effects Clavien score ≥ 3. Results: Mean follow-up were 114 and 124 months for HIFU+ S-EBRT and EBRT + S-HIFU respectively. At 7 years from the primary treatment , the MFSR were significantly better after HIFU first +S- EBRT than after EBRT first+S- HIFU: 96% vs 91%% (p:0.011). The OSR and the CSSR were not significantly different in the two arms (97% and 99% after HIFU+S- EBRT versus 96% and 98% after EBRT+S- HIFU). The HTFR at 7 years was significantly different (p <0.001) after HIFU+ S-EBRT than after EBRT+ S-HIFU 90% versus 69%. In multivariable Cox regression, the initial Gleason sum ≥ 8 and the treatment strategy were predictors of MFSR (risk ratio 3.2 for treatment modality). The rate of side effect Clavien score≥ 3 was significantly higher (p:0.01) in the EBRT+ S-HIFU arm than in the HIFU+ S-EBRT arm. The rate of urinary toxicity (severe incontinence and bladder outlet obstruction) were worse in the EBRT+ S-HIFU arm than in HIFU+S-EBRT arm: 9.4% and 15.2% vs 1.2% and 7.6% (p:0.01 and 0.078). Conclusions: In this single-institution Matched Pair comparison, the MFSR and HTFR were significantly better in the HIFU+S-EBRT arm than in the EBRT+S-HIFU arm. The rate of urinairy toxicity and Clavien≥3 side-effects were Higher in the EBRT + S-HIFU arm than in the HIFU + S-EBRT arm.