Objective To establish, analyze, and screen ideal models based on machine learning algorithms to predict the positive rate of patients who received repeated prostate punctures for guiding clinical decision-making. Methods Clinical data of 281 male patients from multiple centers who underwent at least two consecutive prostate biopsies from January 2008 to December 2022, were retrospectively analyzed, and their first biopsy pathology result was recorded as negative. Key clinical diagnosis and treatment data were recorded for each patient, including BMI, prostate volume, PSA level, fPSA/PSA ratio, PSAD level, complications after the first puncture, pathological results after the first puncture, and strategies used for the two prostate punctures. Statistical analysis was used to analyze the differences in parameters between the final puncture pathology positive group and the negative group. The parameters were trained and fitted through seven machine learning algorithm models such as multivariable logical regression (LR), K-nearest neighbor search (KNN), support vector machine (SVC), decision tree (DT), random forest classifier (RF), naive Bayes classifier (NBC) and gradient enhancement tree (GB). 70% of all data as training set data and 30% of the remaining as verification set data were used for six times cross validation to analyze and compare accuracy and sensitivity, the diagnostic accuracy of each model was evaluated using receiver operating characteristic curve, and its effectiveness in predicting the results of prostate cancer secondary puncture was ultimately evaluated. Results The patients were aged between 32 and 87 years old, with an average of 69. 03 years old. Among the patients, 201 patients were recorded as negative in the final puncture pathology, and 80 patients were recorded as prostate cancer. The inter-group analysis showed that there were significant statistical differences (P <0. 05) in the age of second puncture, volume of first puncture prostate, volume of second puncture prostate, PSA level of second puncture, PSAD of second puncture, and FPSA/PSA ratio of second puncture. All collected data were randomly divided into two parts, such as the training dataset (197 cases, 70% of prostate puncture patients) and the validation dataset (84 cases, the remaining 30%). The results showed that the accuracy rates of LR, KNN, SVC, DT, GNB, RF, and GB in predicting the results of secondary prostate puncture were found to fluctuate between 66. 67% and 74. 88%, the error rates to fluctuate between 21.43% and 34. 29%, the recall rates to fluctuate between 9. 52% and 47. 62%, the specificity to fluctuate between 79. 59 and 97. 96%, the accuracy to fluctuate between 33. 33% and 80. 00%. The specificities of each model (the area under the ROC curve) were found to fluctuate between 0. 568 and 0. 725. Conclusion SVC can more accurately predict the positivity of secondary prostate puncture with fewer parameters. Compared to other algorithm models, it makes the prediction results to have better sensitivity and specificity. Through the collection and training of larger sample size data, it has the potential to become a detection tool with broad compatibility for predicting prostate secondary puncture results. [ABSTRACT FROM AUTHOR]