There have been conflicting studies looking at an association between prostate cancer biochemical recurrence (BCR) after radical prostatectomy (RP) and PDE5i use. Patients completed a 1 – 5 assessment of PDE5i use pre-RP and serially after RP in a prospective, quality of life study evaluating men post-RP. Men who had data on PDE5i use at 3m, 6m, 9m, and 12m in the first year following RP were included in the analysis. The tested predictors of BCR were: age, PSA, Gleason score (G), surgical margin status (SMS), seminal vesicle involvement (SVI), extra capsular extension (ECE), and lymph node involvement (LNI). Predictive nomograms have established these as the important predictors of BCR. PDE5i groups were: low use (never/sometimes) vs. high use (regularly/routinely/more than once a day). Risk groups were low risk (G 6/7 and organ confined disease) or intermediate/high risk (all others). Mean age of the 655 men was 61±7 years. 117 men (18%) had BCR. The mean time to BCR was 1.4±1.4 years. PDE5i groups: 55% low use, 45% high use. There were 16% in the low use PDE5i group with BCR vs 20% in the high use PDE5i group with BCR (RR=1.3: 95% CI: 0.84-1.86, p=0.28). On multivariable analysis, G, SMS, SVI, ECE, and LNI were all associated with BCR (p=0.05 to p=0.001). Age (OR: 1.02, 95% CI: 0.99-1.06, p=0.22), PSA (OR: 1.02, 95% CI: 0.98-1.06, p=0.31), and PDE5i group assignment (OR: 1.52, 95% CI: 0.95-2.43, p=0.08) were not significant predictors in the model. Risk groups were low risk (178 men) and intermediate/high risk (476 men) disease. We could not replicate the analysis with the low risk group since only 5 men had BCR. In the high risk group, there were 112 (23%) who had BCR. The pattern of results for disease characteristics were similar as above. The PDE5i variable, on univariate analysis the group assignment was not significant. There were 22% in the low use PDE5i group with BCR vs 26% in the high use PDE5i group with BCR (RR=1.3: 95% CI: 0.81-1.90, p=0.33). In multivariable analysis, PDE5i group assignment was again not a significant predictor of BCR (OR: 1.37, 95% CI: 0.84-2.22, p=0.20).