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To compare the frequency of airway and respiratory adverse events leading to an intervention between moderate sedation using alfentanil or propofol.We performed a randomized clinical trial in which adults undergoing moderate sedation in the ED received either alfentanil or propofol. Our primary outcome was the frequency of airway and respiratory adverse events leading to an intervention. Other outcomes included sedation depth, efficacy, sedation time, patient satisfaction, pain, and satisfaction.108 subjects completed the trial: 52 receiving alfentanil and 56 receiving propofol. Airway or respiratory adverse events leading to an intervention were similar between the two groups: 23% for alfentanil and 20% for propofol (p = 0.657). There were no serious adverse events in any group. Secondary outcomes were notably different in the rate of reported pain (48% for alfentanil, 13% for propofol) and recall (75% for alfentanil, 23% for propofol) and similar in the rate of satisfaction with the procedure (87% for alfentanil, 84% for propofol).We found a similar frequency of airway and respiratory adverse events leading to intervention between alfentanil and propofol used for moderate procedural sedation. Both agents appear safe for moderate procedural sedation.