Background: PSA produced from prostate cancer (PC) cells escapes proteolytic processing, resulting in a more complexed PSA and a lower %fPSA. Higher %fpsa correlates with lower PC risk. However, the role of fPSA in biochemical recurrence (BCR) after radical prostatectomy (RP) is unknown. Methods: All patients who had BCR after RP and at least one fPSA test, were included. Patients were stratified according to the %fPSA cut-off of 0.15. Multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Results: A total of 81 men with BCR were found (Table 1). Interestingly, 20% (group 1) vs. 60% (groups 2) become castrate resistant (CRPC), p<0.0001 and the time to reach CRPC state was much shorter in group 2 (33.5 months) vs. group 1 (57.9 months), p=0.05. Additionally, 60% of group 2 patients vs. 32.5% of group 1 patients developed metastasis, p=0.014. Lastly, median survival of 193 months for group 2 patients with no median survival for group 1, Log Rank test p=0.023. Multivariable logistic regression analysis demonstrated that secondary Gleason score of 5 (compared to 3) and %fPSA>0.15 predicted CRPC status (OR 11.63, CI 95% 1.38-97.4, p=0.024, OR 7.99, CI 95% 2-31.95, p=0.003, respectively). Conclusions: %fPSA>0.15 in the setting of BCR confers a more aggressive disease, manifesting in a faster development of CRPC, metastasis and death. Our findings suggest a reversal in the significance of % fPSA values in BCR patients, and should be validated in larger cohorts.