BACKGROUND Hypoxemia can occur during upper gastrointestinal endoscopy with or without pharmacologic sedation. We investigated possible predictive factors of severe oxygen desaturation (SaO2 < 90%) in nonsedated patients undergoing endoscopy. METHODS A total of 481 patients who underwent upper gastrointestinal endoscopy without sedation were monitored with continuous pulse oximetry. Multivariate logistic regression analysis was used to identify factors related to the patient, the examination, and the monitoring data that would predict severe desaturation. RESULTS Mild desaturation (SaO2 between 90% and 94%) was found in 23.7% of the patients, and severe desaturation (SaO2 < 90%) was found in 6.4%. The variables found to predict severe desaturation were basal SaO2 < 95% (odds ratio 67.7), respiratory disease (odds ratio 30.5), more than one attempt needed for intubation (odds ratio 39.4), emergency procedure (odds ratio 14.9), and American Society of Anesthesiologists score of III or IV (odds ratio 3.9). CONCLUSIONS The predictive variables analyzed in this study can be used to identify patients who are at increased risk for desaturation. Such patients require very close monitoring (pulse oximetry at a minimum). Endoscopists and assistants should be especially alert to the possibility of respiratory depression in these patients.