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INTRODUCTION: Controversy exists regarding testosterone replacement therapy (TRT) in men following radical prostatectomy (RP). Many clinicians are hesitant to offer patients TRT after an RP, out of concern that the increased androgen levels may promote tumor progression or recurrence from residual tumor. Recently, several small studies have demonstrated the use of TRT in men following an RP and have shown an improvement in serum testosterone levels with no increase in prostate-specific antigen (PSA) values. AIMS: The aim of this article is to assess changes in PSA and testosterone values in hypogonadal patients on TRT after RP and also to evaluate the impact of pathologic Gleason grade on ultimate PSA values. METHODS: All hypogonadal men who were treated with TRT by members of our department following RP were retrospectively reviewed. PSA values before RP, after RP, and after TRT were evaluated. Serum testosterone levels before and after TRT were also examined. Only patients with undetectable PSA values and negative surgical margins on pathologic specimen were offered TRT and included in the study. MAIN OUTCOME MEASURES: Main outcome measures were changes in PSA and testosterone values after initiation of TRT. RESULTS: Fifty-seven men, ages 53-83 years (mean 64), were identified as having initiated TRT following RP. Men received TRT for an average of 36 months following RP (range 1-136 months). Patients were followed an average of 13 months after initiation of TRT (range 1-99 months). The mean testosterone values rose from 255 ng/dL before TRT to 459 ng/dL after TRT (P < 0.001). There was no increase in PSA values after initiation of TRT and thus no patient had a biochemical PSA recurrence. CONCLUSION: TRT is effective in improving testosterone levels, without increasing PSA values, in hypogonadal men who have undergone RP.