Background: Despite low mortality for elective procedures in the United States and developed countries, some patients have unexpected care escalations (UCE) following post-anesthesia care unit (PACU) discharge. Studies indicate patient risk factors for UCE, but determining which factors are most important is unclear. Machine learning (ML) can predict clinical events. We hypothesized that ML could predict patient UCE after PACU discharge in surgical patients and identify specific risk factors. Methods: We conducted a single center, retrospective analysis of all patients undergoing non-cardiac surgery (elective and emergent). We collected data from pre-operative visits, intra-operative records, PACU admissions, and the rate of UCE. We trained a ML model with this data and tested the model on an independent data set to determine its efficacy. Finally, we evaluated the individual patient and clinical factors most likely to predict UCE risk. Results: Our study revealed that ML could predict UCE risk which was approximately 5% in both the training and testing groups. We were able to identify patient risk factors such as patient vital signs, emergent procedure, ASA Status, and non-surgical anesthesia time as significant variable. We plotted Shapley values for significant variables for each patient to help determine which of these variables had the greatest effect on UCE risk. Of note, the UCE risk factors identified frequently by ML were in alignment with anesthesiologist clinical practice and the current literature. Conclusions: We used ML to analyze data from a single-center, retrospective cohort of non-cardiac surgical patients, some of whom had an UCE. ML assigned risk prediction for patients to have UCE and determined perioperative factors associated with increased risk. We advocate to use ML to augment anesthesiologist clinical decision-making, help decide proper disposition from the PACU, and ensure the safest possible care of our patients.