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Background Monitored anesthesia care (MAC) and general anesthesia (GA) are the 2 most common methods of sedation used for endoscopic retrograde cholangiopancreatography (ERCP). We performed a systematic review and meta-analysis to compare the overall safety between MAC vs. GA in ERCP. Methods We conducted a comprehensive search of electronic databases to identify studies reporting the use of MAC or GA as a choice of sedation for ERCP. The primary outcome was to compare the overall rate of sedation-related adverse events in MAC vs. GA groups. The secondary endpoint was to investigate the total duration of the procedure, recovery time, ERCP cannulation rates, and conversion rate of MAC to GA. The meta-analysis was performed using a Der Simonian and Laird random-effects model. Results A total of 21 studies reporting on 11,592 patients were included. The overall sedationrelated side-effects were similar in the GA (12.76%, 95% confidence interval [CI] 5.80-21.73; I2=95%) and MAC (12.08%, 95%CI 5.38-20.89; I2=99%) groups (P=0.956). Hypoxia, arrhythmias, hypotension, aspiration and other sedation-related side-effects were similar between the 2 groups. The mean duration of the procedure was longer in the MAC group, but the mean recovery time was shorter. Significant heterogeneity was noted in our meta-analysis. Conclusions In our meta-analysis, the overall sedation-related side-effects were similar between the MAC and GA groups. MAC could be used as a safer alternative to GA when performing ERCP. However, large multicenter randomized control trials are needed to further validate our findings. [ABSTRACT FROM AUTHOR]