BACKGROUND: Postoperative length of stay is a key indicator in the management of medical resources and an indirect predictor of the incidence of surgical complications and the degree of recovery of the patient after cancer surgery. Recently, machine learning has been used to predict complex medical outcomes, such as prolonged length of hospital stay, using extensive medical information. OBJECTIVE: The objective of this study was to develop a prediction model for prolonged length of stay after cancer surgery using a machine learning approach. METHODS: In our retrospective study, electronic health records (EHRs) from 42,751 patients who underwent primary surgery for 17 types of cancer between January 1, 2000, and December 31, 2017, were sourced from a single cancer center. The EHRs included numerous variables such as surgical factors, cancer factors, underlying diseases, functional laboratory assessments, general assessments, medications, and social factors. To predict prolonged length of stay after cancer surgery, we employed extreme gradient boosting classifier, multilayer perceptron, and logistic regression models. Prolonged postoperative length of stay for cancer was defined as bed-days of the group of patients who accounted for the top 50% of the distribution of bed-days by cancer type. RESULTS: In the prediction of prolonged length of stay after cancer surgery, extreme gradient boosting classifier models demonstrated excellent performance for kidney and bladder cancer surgeries (area under the receiver operating characteristic curve [AUC] >0.85). A moderate performance (AUC 0.70-0.85) was observed for stomach, breast, colon, thyroid, prostate, cervix uteri, corpus uteri, and oral cancers. For stomach, breast, colon, thyroid, and lung cancers, with more than 4000 cases each, the extreme gradient boosting classifier model showed slightly better performance than the logistic regression model, although the logistic regression model also performed adequately. We identified risk variables for the prediction of prolonged postoperative length of stay for each type of cancer, and the importance of the variables differed depending on the cancer type. After we added operative time to the models trained on preoperative factors, the models generally outperformed the corresponding models using only preoperative variables. CONCLUSIONS: A machine learning approach using EHRs may improve the prediction of prolonged length of hospital stay after primary cancer surgery. This algorithm may help to provide a more effective allocation of medical resources in cancer surgery.