Abstract:Background: Postoperative nausea and vomiting (PONV) is a frequently observed complication in patients undergoing surgery under general anesthesia. Moreover, it is a frequent cause of distress and dissatisfaction during the early postoperative period. The tools used for predicting PONV at present have not yielded satisfactory results. Therefore, prognostic tools for the prediction of early and delayed PONV were developed in this study with the aim of achieving satisfactory predictive performance. Methods: The retrospective data of adult patients admitted to the post-anesthesia care unit after undergoing surgical procedures under general anesthesia at the Sheba Medical Center, Israel, between September 1, 2018, and September 1, 2023, were used in this study. An ensemble model of machine learning algorithms trained on the data of 54848 patients was developed. The k-fold cross-validation method was used followed by splitting the data to train and test sets that optimally preserve the sociodemographic features of the patients, such as age, sex, and smoking habits, using the Bee Colony algorithm. Findings: Among the 54848 patients, early and delayed PONV were observed in 2706 (4.93%) and 8218 (14.98%) patients, respectively. The proposed PONV prediction tools could correctly predict early and delayed PONV in 84.0% and 77.3% of cases, respectively, outperforming the second-best PONV prediction tool (Koivuranta score) by 13.4% and 12.9%, respectively. Feature importance analysis revealed that the performance of the proposed prediction tools aligned with previous clinical knowledge, indicating their utility. Interpretation: The machine learning-based tools developed in this study enabled improved PONV prediction, thereby facilitating personalized care and improved patient outcomes.