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Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy.We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT.Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8–18.1) ADT). Median SRT dose was 70 Gy (IQR 70–70), and median follow-up after SRT was 6.7 years (IQR 4.5–10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42–0.86; P = 0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ≥ 0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P = 0.003), but not for men with favorable disease (81.2% vs 78.0%; P = 0.971).The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ≥0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA < 0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesisgenerating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.