Objective:The aim of this study was to evaluate the diagnostic performance of multiparametric magnetic resonance imaging for clinically significant prostate cancer and to determine whether applying Prostate Imaging Reporting and Data Systems version 2.1 score could improve the diagnostic pathway besides the biochemical characteristics.Materials and methods:In this study, 199 patients with clinically suspected prostate cancer who underwent multiparametric magnetic resonance imaging were included. Logistic regression analyses and receiver operating characteristic curve were performed to determine independent predictors and to compare diagnostic performance of indicators for clinically significant prostate cancer. Two models were established. In model 1, the diagnostic performance of prostate-specific antigen- and prostate-specific antigen density-derived parameters were evaluated. In model 2, the prediction potential of model 1 plus Prostate Imaging Reporting and Data Systems version 2.1 score was analyzed.Results:Sixty-four patients were positive for clinically significant prostate cancer by histopathological analysis (32.1%). In model 1, a prostate-specific antigen density >0.15 was labeled as the strongest predictor of malignancy. In model 2, a prostate-specific antigen density >0.15, a Prostate Imaging Reporting and Data Systems score ≥3, and a Prostate Imaging Reporting and Data Systems score ≥4 demonstrated the strongest association with malignancy. Among these parameters, a Prostate Imaging Reporting and Data Systems score ≥4 (P= .003) was found to be the most robust predictor for malignancy, followed by a Prostate Imaging Reporting and Data Systems score ≥3 (P= .012). The multivariate analysis revealed higher accuracy in model 2 (76.9%) than in model 1 (67.8%). The area under curve values with respect to prostate-specific antigen, prostate-specific antigen density, model 1, and model 2 were 0.632, 0.741, 0.656, and 0.798, respectively.Conclusion:These results indicated that Prostate Imaging Reporting and Data Systems version 2.1 score and prostate-specific antigen density are independent predictors for the presence of clinically significant prostate cancer. Both prostate-specific antigen density and Prostate Imaging Reporting and Data Systems version 2.1 score should be risen to prominence in the decision of biopsy instead of PSA.