Objectives. To determine the probability of biochemical control for patients treated with salvage irradiation and identify prognostic factors associated with successful salvage. The optimal management of prostate cancer in patients with an elevated prostate-specific antigen (PSA) level after radical prostatectomy remains unclear. Methods. We reviewed the records of 54 patients with node-negative prostate cancer treated with radiotherapy alone between 1991 and 1998 for isolated biochemical relapse after prostatectomy. The median preoperative PSA level was 15 ng/mL, and the median salvage PSA level was 1.3 ng/mL. Complete pathologic information was recorded, as was the interval to postoperative PSA failure. Radiotherapy was delivered to the prostatic fossa using appropriate techniques. The primary endpoint was biochemical failure, measured from radiotherapy initiation to the first detectable PSA level. Biochemical control rates were determined using Kaplan-Meier methods. The median follow-up was 45 months. Results. The initial complete response rate was 76%. Only seminal vesicle status demonstrated borderline significance for the rate of the initial complete response. The 5-year actuarial biochemical control rate was 35%. The presence of seminal vesicle invasion, Gleason score greater than 6, and an immediately detectable postoperative PSA level all predicted for decreased 5-year biochemical control. Gleason score and detectable postoperative PSA retained significance on multivariate analysis. Those with a salvage PSA level of 1.2 ng/mL or less had a trend toward a decreased 5-year biochemical control rate ( P = 0.07). Conclusions. Salvage radiotherapy yields a 76% complete response rate, with 35% of treated patients free of a detectable PSA at 5 years. Those with favorable biochemical and pathologic tumor features are most likely to remain disease free.