AIM To evaluate the anesthetic effect of esketamine combined with remimazolam in elderly patients undergoing gastroenteroscopy, as well as the influence on oxygen desaturation saturation and hemodynamics. METHODS A total of 160 elderly patients scheduled to undergo gastroenteroscopy in our hospital from September 2021 to October 2023 were included, and randomly equally divided into remimazolam group (R group) or esketamine combined remimazolam group (E+R group). Both two groups received intravenous injection of sufentanil 0.1 μg·kg^-1 and remimazolam 0.2 mg·kg^-1 for anesthesia induction. The E+R group additionally was given intravenous esketamine 0.25 mg·kg^-1. The primary outcomes during the examination include occurrence of desaturation and hypotension. Secondary outcomes include hemodynamic parameters during the examination, rescue sedation, time to loss of consciousness, time to recovery of consciousness, and PACU stay time. The MAP and HR are recorded at different time points: before anesthesia induction (T₀), immediately after anesthesia induction (T₁), immediately after the placement of gastroscopy (T₂), immediately after the placement of colonoscopy (T₃), and immediately after the surgery (T₄). The PACU outcome include nausea/vomiting, dizziness/headache, delayed awakening, emergence agitation, and patient satisfaction scores. RESULTS There were 78 and 80 patients included eventually in the E+R group and the R group, respectively. The rates of deoxygenation saturation, hypotension and remedial sedation ≥2 times in the E+R group were significantly lower than those in the R group (P<0.05). The loss time of consciousness, recovery time of consciousness and PACU residence time in the E+R group were significantly shorter than those in the R group (P<0.05). MAP and HR of T₁-T₃ time points in the E+R group were significantly higher than those in the R group (P<0.05). The MAP and HR of T₂ and T₃ were significantly higher than those of T₁ in the R group (P<0.05), but there was no significant difference between MAP and HR of T₂ or T₃ and those of T₁ in the E+R group (P>0.05). There were no significant differences in PACU nausea and vomiting, dizziness/headache, delayed recovery, emergence agitation and satisfaction scores between the two groups (P>0.05). CONCLUSION Compared with remimazolam, esketamine combined with remimazolam can shorten the recovery time, reduce the incidence of desaturation and hypotension in elderly patients undergoing gastroenteroscopy, and contribute to maintain hemodynamic stability without increasing adverse reactions during recovery.