Background: Historically, the use of testosterone replacement therapy (TRT) has not been recommended in men with a history of prostate cancer (PC). However, low testosterone levels are significantly associated with metabolic complications, decreased sexual function, and (more recently) high-grade PC. In 2009, in hopes of improving sexual function outcomes in men following radical prostatectomy (RP), we began treating low-risk patients with TRT. The current study examines the impact of TRT on biochemical recurrence (BCR). Methods: Between December 2009 and June 2018, a cohort of 850 patients underwent RP by a single surgeon. 152 (18%) men were postoperatively placed on TRT for recovery of sexual function. All data was prospectively collected and retrospectively analyzed. TRT patients were proportionately matched to 419 control patients by pathologic Gleason Grade Group (GGG) and stage. Univariate and multivariate comparisons were used to compare rates and time to BCR (two consecutive PSAs ≥ 0.2 ng/dl); Cox regression modeling was used to generate a survival function at the mean of covariates. Results: There were no statistically significant differences in preoperative PSA, age, prostate weight, pathologic GGG and stage between the control versus TRT groups. Median follow-up time was 3 years in both groups. 7/152 (4.6%) and 39/419 (9.3%) patients experienced BCR in the TRT versus control groups, respectively (unadjusted, p=0.068). In adjusted time to-analysis, TRT was an independent predictor of recurrence-free survival, after controlling for GGG, p-stage, preoperative FT and PSA. A patient on TRT was approximately 53% less likely to experience a BCR (OR: 0.534, 95%CI: 0.288-0.993). Conclusions: After accounting for pathologic GGG, stage, and other significant covariates, the use of TRT independently reduced recurrence post-RP. These results suggest the need for a multi-center randomized control trial.