BACKGROUND: Remimazolam is a novel ultra-short-acting sedative, but its safety and adverse events (AEs) in high-risk patients in the intensive care unit (ICU) setting remain unknown. METHODS:This was a single-center, retrospective study that compared remimazolam to propofol and midazolam in patients undergoing upper gastrointestinal endoscopy. The primary outcome was the incidence of treatment-related AEs. The secondary outcomes were the time to extubation, the length of ICU stay, and the average cost of sedative per case. RESULTS:Of the 88 patients analyzed, 47 were treated with remimazolam (mean dose, 7.90±4.84 mg), and 41 were treated with propofol (21.19±17.98 mg) or midazolam (3.08±2.17 mg). There was no statistically significant difference in the average duration of the endoscopic procedure (35.89±13.37 min vs. 44.51±21.68 min, P=0.133) or the time to extubation (15.00±9.75 h vs. 20.59±18.71 h, P=0.211) in the remimazolam group (group I) compared to the propofol or midazolam group (group II). ICU stays (5.40±2.93 d vs. 4.63±3.31 d, P=0.072) and treatment-related AEs (48.61% vs. 51.38%, P=0.056) were similar between groups. The average cost of sedative per case was signifi cantly lower in the group I than in the group II (RMB 16.07±10.58 yuan vs. RMB 24.37±15.46 yuan, P=0.016).CONCLUSION: Remimazolam-based sedation was noninferior to the classic sedatives and had lower average cost per case, indicating that it may be used as a promising sedative for high-risk patients during endoscopic procedures in the ICU setting.