The diagnostic performance of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) has been challenged due to its lower diagnostic accuracy and higher false-positive rates for prostate cancer detection. This study aimed to analyze the diagnostic performance of PI-RADS v2 in combination with clinical parameters in patients with suspected prostate cancer.A total of 424 men with suspicion of prostate cancer were retrospectively analyzed. Logistic regression analyses were performed to identify predictors of clinically significant prostate cancer defined as a Gleason score of 3 + 4 or greater. The prediction performance was compared with prostate specific antigen (PSA), free/total PSA ratio (f/t PSA), PSA density (PSAD), PI-RADS v2 alone, and PI-RADS v2 plus PSAD using receiver operating characteristics (ROCs).In total, 231 out of 424 cases (54.48%) were pathologically diagnosed as prostate cancer. The percentage of clinically significant prostate cancer was higher in patients with PI-RADS v2 score of 4 or greater compared to PI-RADS v2 score of less than 4 (90.86% vs. 55.88%, P < 0.001). Age, PSA level, f/t PSA, PSAD, and PI-RADS v2 were significant independent predictors of clinically significant prostate cancer. The ROC area under the curve of PI-RADS v2 plus PSAD (0.952) was larger compared with PSA (0.845), f/t PSA (0.719), PSAD (0.920), and PI-RADS v2 alone (0.885).PI-RADS v2 in combination with PSAD may help detect clinically significant prostate cancer and provide benefit in making the decision to biopsy men at suspicion of prostate cancer.