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Background/Aims: Recent studies have demonstrated that etomidate is a safe sedative drug with noninferior sedative effects. In our recent study, we revealed that etomidate/midazolam was more hemodynamically stable than propofol/midazolam in elderly patients undergoing colonoscopies. We aimed to investigate whether compared with propofol/midazolam, etomidate/midazolam causes fewer cardiopulmonary adverse events with noninferior efficacy for screening colonoscopies in patients of all ages. Methods: In this single-center, randomized, double-blind study, we prospectively enrolled 200 patients. The patients were divided into etomidate and propofol groups. The primary outcome was the occurrence of cardiopulmonary adverse events. The secondary outcomes were the proportion of patients with fluctuations in vital signs (oxygen desaturation and transient hypotension), adverse events interrupting the procedure, and sedation-related outcomes. Results: Adverse cardiopulmonary events were more common in the propofol group than the etomidate group (65.0% vs 51.0%, respectively; p=0.045). Forty-six patients (46.0%) in the propofol group and 29 (29.0%) in the etomidate group experienced fluctuations in their vital signs (p=0.013). The proportions of patients experiencing adverse events that interrupted the procedure, including myoclonus, were not significantly different between the two groups (etomidate: 20.0% vs propofol: 11.0%; p=0.079). Both groups had similar sedation-related outcomes. Multivariate analysis revealed that compared with the propofol groups, the etomidate group had a significantly lower risk of fluctuations in vital signs (odds ratio, 0.427; 95% confidence interval, 0.230 to 0.792; p=0.007). Conclusions: Compared with using propofol/midazolam, using etomidate/midazolam for screening colonoscopies results in more stable hemodynamic responses in patients of all ages; therefore, we recommend using etomidate/midazolam for colonoscopies in patients with cardiovascular risk factors.