BackgroundUnplanned post-operative reintubation (UPR) is a complication of general anesthesia (GA) that can be associated with worsened outcomes.ObjectiveEvaluate characteristics associated with UPR in patients undergoing procedures under GA.MethodsPatients over the age of 18 undergoing surgical procedures under GA were extracted from our institution's electronic medical record. Patient baseline, procedural, and anesthesia characteristics were evaluated for associations with UPR.ResultsIn 29,284 surgical procedures undergoing GA, there were 29 (0.1%) patients that required UPR. The most common surgical service with UPR was otolaryngology; the most common surgical positioning was supine. When controlling for operative time and case complexity, UPR was predicted by high-dose opioids, defined as opioid administration greater than the 75th percentile of our institutional cohort. Prolonged operative time, estimated blood loss (EBL), body mass index (BMI), extubation time after reversal, or age were not independently associated with UPR.ConclusionOur analysis revealed that high-dose opioid administration is independently associated with intraoperative UPR. Awareness of patients at the highest risk for UPR along with provider education regarding techniques to avoid respiratory depression in this patient population is essential in reducing patient morbidity and mortality. This knowledge will help guide perioperative physicians in medical optimization, appropriate selection of intraoperative analgesics, and cautious extubation criteria to ensure patient safety.