Abstract Objectives To predict the rate of prostate cancer detection on prostate biopsy more accurately, the performance of deep learning utilizing a multilayer artificial neural network was investigated. Materials and methods A total of 334 patients who underwent multiparametric magnetic resonance imaging before ultrasonography-guided transrectal 12-core prostate biopsy were enrolled in the analysis. Twenty-two non-selected variables as well as selected ones by least absolute shrinkage and selection operator (Lasso) regression analysis and by stepwise logistic regression analysis were input into the constructed multilayer artificial neural network (ANN) programs. 232 patients were used as training cases of ANN programs, and the remaining 102 patients were for the test to output the probability of prostate cancer existence, accuracy of prostate cancer prediction, and area under the receiver operating characteristic (ROC) curve with the learned model. Results With any prostate cancer objective variable, Lasso and stepwise regression analyses selected 12 and 9 explanatory variables from 22, respectively. In common between them, age at biopsy, findings on digital rectal examination, findings in the peripheral zone on MRI diffusion-weighted imaging, and body mass index were positively influential variables, while numbers of previous prostatic biopsy and prostate volume were negatively influential. Using trained ANNs with multiple hidden layers, the accuracy of predicting any prostate cancer in test samples was about 5-10% higher compared with that with logistic regression analysis (LR). The AUCs with multilayer ANN were significantly larger on inputting variables that were selected by the stepwise logistic regression compared with the AUC with LR. The ANN had a higher net-benefit than LR between prostate cancer probability cut-off values of 0.38 and 0.6. Conclusion ANN accurately predicted prostate cancer without biopsy marginally better than LR. However, for clinical application, ANN performance may still need improvement.