Objective: To test the diagnostic performance of percent free prostate-specific antigen (% fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China. Methods: Consecutive patients with a PSA of 4.0e10.0 ng./mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, % fPSA, and % fPSA in combination with PSA (% fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Results: A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng./mL were included, and the detection rate of PCa was 25.1%. The AUC of % fPSA and % fPSA + PSA in predicting any PCa was superior to PSA alone in men aged >= 60 years (0.623 vs. 0.534, p < 0.0001) but not in men aged 40e59 years (0.517 vs. 0.518, p = 0.939). Similar result was yield in predicting HGPCa. Conclusion: In a clinical setting of Chinese men with 4.0e10.0 ng./mL PSA undergoing initial prostate biopsy, adding % fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients >= 60 but not in patients aged 40 -59 years. (C) 2015 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license.