Objective To investigate the effects of remimazolam and propofol sedation on the quality of recovery after painless colonoscopy, especially the recovery of cognitive function. Methods A total of 248 patients undergoing colonoscopy were selected. According to the random number table method, they were divided into two groups (n=124): a remimazolam group (group R) and propofol group (group P). Both groups were intravenously injected with fentanyl 1 μg/kg, then group R was treated with remimazolam at an initial dose of 5.0 mg followed by a supplementary dose of 2.5 mg, while group P was treated with propofol at an initial dose of 1.5 mg/kg followed by a supplementary dose of 0.5 mg/kg. The quality of recovery was evaluated with the Postoperative Quality of Recovery Scale (PostopQRS) before examination and 15 min, 40 min, 1 day, 3 days, 7 days and 3 months after examination. The rate of the overall recovery and its domains (physiological, nociceptive, emotive, activities of daily living and cognitive function) in both groups at different time points were recorded. The times of additional induction, the times of supplementary sedation, the modified Observer's Assessment Alert/Sedation (mOAA/S) score after induction, sedation induction time, sedation duration, colonoscopy duration, dosage of fentanyl, time to eye‑opening and time to discharge from the postanesthesia care unit (PACU) in both groups were recorded. The incidences of adverse events (hypotension, bradycardia, hypoxemia, injection site pain, dizziness, abnormal gait, nausea and vomiting) were recorded. The patient satisfaction toward anesthesia effect and endoscopist satisfaction toward surgical conditions were recorded. Results On day 1 after colonoscopy, group R showed non‑inferior cognitive recovery, compared with group P [87.6% vs 81.8%, risk difference 5.8%, (95%CI ‒3.97%,15.48%)]. According to the Generalized Estimation Equation (GEE) analysis, the rate of cognitive recovery on days 1 and 7 and the overall recovery rate on day 7 in group R were higher than those in group P (P<0.05). There was no statistical difference in the rates of physiological, nociceptive, emotive and activities of daily living recovery between the two groups at each time point (P>0.05). Group R presented increases in the times of additional induction and times of supplementary sedation (P<0.05), the mOAA/S score after induction (P<0.05), and the sedation induction time and time to eye‑opening, compared with group P (P<0.05). There was no statistical difference in sedation duration, colonoscopy duration, dosage of fentanyl and time to discharge from the PACU between the two groups (P>0.05). The incidences of hypotension, hypoxemia and injection site pain in group R were lower than those in the group P (P<0.05). There were no statistical differences in the incidences of bradycardia, dizziness, abnormal gait, nausea and vomiting between the two groups (P>0.05). The endoscopist satisfaction toward surgical conditions in group P was higher than that in group R (P<0.05). There was no statstical difference in patient satisfaction twoard anesthesia effect between the two groups (P>0.05). Conclusions Compared with propofol, remimazolam exhibits non‑inferior cognitive recovery and overall recovery in patients undergoing colonoscopy. Remimazolam is associated with a lower incidence of hypoxemia and hypotension. Endoscopist satisfaction is better when propofol is used.