AimsAdvanced age is an important risk factor for adverse events during procedural sedation. Remimazolam is safe and effective in gastroscopic sedation. However, the ideal dose and application for older patients are not well known. We aim to investigate its 95% effective dose (ED95) for older patients undergoing gastroscopy and to assess its safety and efficacy, with propofol as the comparison.MethodsThe trial consists of 2 parts, patients aged >65 years and scheduled for outpatient painless gastroscopy were enrolled. In the first part, Dixon's up‐and‐down methodology was used to determine the ED95 of remimazolam besylate and propofol for gastroscopic insertion, in combination with 0.2 μg/kg remifentanil. In the second part, patients in each group received 0.2 μg/kg remifentanil and ED95 dose of the study drugs for sedation induction, supplemental doses were added to maintain sedation depth when necessary. The primary outcome was the incidence of adverse events. The secondary outcome was the recovery time.ResultsThe ED95 of remimazolam besylate and propofol induction were 0.2039 (95% confidence interval 0.1753–0.3896) mg/kg and 1.9733 (95% confidence interval 1.7346–3.7021) mg/kg respectively. Adverse events were reported in 26 (40.6%) patients in the remimazolam group and 54 (83.1%) in the propofol group (P < .0001), whereas the remimazolam group presented a higher incidence of hiccups (P = .0169). Besides, the median time to awakening was approximately 1 min shorter with remimazolam than with propofol (P < .05).ConclusionFor older patients undergoing gastroscopy, the ED95 dose of remimazolam is a safer alternative than propofol when inducing the same sedation depth.