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Background/Aims: Combination of midazolam and opioids is used widely for endoscopic sedation. Compared with meperidine, fentanyl is reportedly associated with rapid recovery, turnover rate of endoscopy room, and quality of endoscopy. We compared fentanyl with meperidine when combined with midazolam for sedative colonoscopy. Methods: A retrospective, cross-sectional, 1:2 matching study was conducted. Induction and recovery time were compared as theprimary outcomes. Moreover, cecal intubation time, withdrawal time, total procedure time of colonoscopy, paradoxical reaction, adenoma detection rate, and adverse effect of midazolam or opioids were assessed as the secondary outcomes. Results: A total of 129 subjects (43 fentanyl vs. 86 meperidine) were included in the analysis. The fentanyl group showed significantlymore rapid induction time (4.5±2.7 min vs. 7.5±4.7 min, p<0.001), but longer recovery time (59.5±25.6 min vs. 50.3±10.9 min,p=0.030) than the meperidine group. In multivariate analysis, the induction time of the fentanyl group was 3.40 min faster (p<0.001),but the recovery time was 6.38 min longer (p=0.046) than that of the meperidine group. There was no difference in withdrawal timeand adenoma detection rate between the two groups. Conclusions: The fentanyl group had more rapid sedation induction time but longer recovery time than the meperidine group.