Background and Study AimAlthough propofol is widely used for sedation for endoscopic procedures, concerns remain regarding cardiopulmonary adverse events. Etomidate has little effect on the cardiovascular and respiratory systems, but patient satisfaction analysis is lacking. We compared the efficacy and safety of balanced propofol and etomidate sedation during advanced endoscopic procedures.MethodsAs a randomized noninferiority trial, balanced endoscopic sedation was achieved using midazolam and fentanyl, and patients were randomly assigned to receive propofol (BPS) or etomidate (BES) as add-on drug. The main outcomes were sedation efficacy measured on a 10-point visual analog scale (VAS) and safety.ResultsIn total, 186 patients (94 in the BPS group and 92 in the BES group) were evaluated. BES did not show noninferiority in terms of overall patient satisfaction, with a difference in VAS score of −0.35 (97.5 % confidence interval −1.03 to ∞, p = 0.03). Among endoscopists and nurses, BES showed noninferiority to BPS, with differences in VAS scores of 0.06 and 0.08, respectively. Incidence of cardiopulmonary adverse events was lower in the BES group (27.7 versus 14.1 %, p = 0.023). Hypoxia occurred in 5.3 and 1.1 % of patients in the BPS and BES group (p = 0.211). Myoclonus occurred in 12.1 % (11/92) in the BES group. BES had lower risk of overall cardiopulmonary adverse events (odds ratio 0.401, p = 0.018).ConclusionsBES was not noninferior to BPS in terms of patient satisfaction. However, BES showed better safety outcomes in terms of cardiopulmonary adverse events.