OBJECTIVE Although the combination of midazolam-meperidine has been widely used as a sedation regimen for colonoscopy, its residual effect which is longer than the duration of a colonoscopy procedure can delay patient recovery and discharge. Remifentanil, an ultra-short-acting opioid, has a very brief duration of action. We hypothesized that using remifentanil alone for colonoscopy would provide shorter recovery time compared with the midazolam-meperidine combination. METHODS Time to achieve Aldrete score = 10 was determined and compared in patients who were randomly allocated to receive remifentanil alone (group-R, n = 27) or a midazolam-meperidine combination (group-MM, n = 27) for colonoscopy. Intergroup differences in sedation, recall analgesia, cardio-respiratory profiles, and satisfaction of patient and endoscopist were also determined during and after colonoscopy. RESULTS Group-R showed a significantly shorter recovery time than group-MM (median [25-75%], 0 [0-10] vs 30 [15-30] min, P < 0.001). Group-R showed significantly higher bispectral-index values during colonoscopy (92 [85-96] vs 84 [80-87], P = 0.001); a higher incidence of recall of explanations given during and after colonoscopy (100 vs 48% and 96 vs 52%, both P < 0.001); and a lower distress score (visual analog scale 30/100 vs 37/100 mm, P = 0.002), than did group-MM. Neither extent of pain, incidence of hemodynamic instability nor incidence of respiratory depression differed between the groups. CONCLUSIONS Remifentanil for colonoscopy afforded faster recovery compared to midazolam-meperidine combination. It also provided greater patient-endoscopist communication and satisfaction with comparable patient analgesia and cardiorespiratory profile during colonoscopy.