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Abstract Background Machine learning has many attractive theoretic properties, specifically, the ability to handle non predefined relations. Additionally, studies have validated the clinical utility of mpMRI for the detection and localization of CSPCa (Gleason score ≥ 3 + 4). In this study, we sought to develop and compare machine-learning models incorporating mpMRI parameters with traditional logistic regression analysis for prediction of PCa (Gleason score ≥ 3 + 3) and CSPCa on initial biopsy. Methods A total of 688 patients with no prior prostate cancer diagnosis and tPSA ≤ 50 ng/ml, who underwent mpMRI and prostate biopsy were included between 2016 and 2020. We used four supervised machine-learning algorithms in a hypothesis-free manner to build models to predict PCa and CSPCa. The machine-learning models were compared to the logistic regression analysis using AUC, calibration plot, and decision curve analysis. Results The artificial neural network (ANN), support vector machine (SVM), and random forest (RF) yielded similar diagnostic accuracy with logistic regression, while classification and regression tree (CART, AUC = 0.834 and 0.867) had significantly lower diagnostic accuracy than logistic regression (AUC = 0.894 and 0.917) in prediction of PCa and CSPCa (all P