Low anterior resection syndrome (LARS) severely impairs patient postoperative quality of life, especially major LARS. However, there are few tools that can accurately predict major LARS in clinical practice.To develop a machine learning model using preoperative and intraoperative factors for predicting major LARS following laparoscopic surgery of rectal cancer in Chinese populations.Clinical data and follow-up information of patients who received laparoscopic anterior resection for rectal cancer from two medical centers (one discovery cohort and one external validation cohort) were included in this retrospective study. For the discovery cohort, the machine learning prediction algorithms were developed and internally validated. In the external validation cohort, we evaluated the trained model using various performance metrics. Further, the clinical utility of the model was tested by decision curve analysis.Overall, 1651 patients were included in the present study. Anastomotic height, neoadjuvant therapy, diverting stoma, body mass index, clinical stage, specimen length, tumor size, and age were the risk factors associated with major LARS. They were used to construct the machine learning model to predict major LARS. The trained random forest (RF) model performed with an area under the curve of 0.852 and a sensitivity of 0.795 (95%CI: 0.681-0.877), a specificity of 0.758 (95%CI: 0.671-0.828), and Brier score of 0.166 in the external validation set. Compared to the previous preoperative LARS score model, the current model exhibited superior predictive performance in predicting major LARS in our cohort (accuracy of 0.772 for the RF model vs 0.355 for the preoperative LARS score model).We developed and validated a robust tool for predicting major LARS. This model could potentially be used in the clinic to identify patients with a high risk of developing major LARS and then improve the quality of life.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.