High rates of inappropriate use of surgical antimicrobial prophylaxis were reported in many countries. Auditing the prophylactic antimicrobial use in enormous medical records by manual review is labor-intensive and time-consuming. The purpose of this study is to develop accurate and efficient machine learning models for auditing appropriate surgical antimicrobial prophylaxis. The supervised machine learning classifiers (Auto-WEKA, multilayer perceptron, decision tree, SimpleLogistic, Bagging,

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... d AdaBoost) were applied to an antimicrobial prophylaxis dataset, which contained 601 instances with 26 attributes. Multilayer perceptron, SimpleLogistic selected by Auto-WEKA, and decision tree algorithms had outstanding discrimination with weighted average AUC > 0.97. The Bagging and SMOTE algorithms could improve the predictive performance of decision tree against imbalanced datasets. Although with better performance measures, multilayer perceptron and Auto-WEKA took more execution time as compared with that of other algorithms. Multilayer perceptron, SimpleLogistic, and decision tree algorithms have outstanding performance measures for identifying the appropriateness of surgical prophylaxis. The efficient models developed by machine learning can be used to assist the antimicrobial stewardship team in the audit of surgical antimicrobial prophylaxis. In future research, we still have the challenges and opportunities of enriching our datasets with more useful clinical information to improve the performance of the algorithms.