Background: Endoscopic retrograde cholangiography and endoscopic sphincterotomy (ES) with subsequent cholecystectomy is the standard of care for the management of patients with choledocholithiasis. There is conflicting evidence in terms of mortality reduction, prevention of complications specifically biliary pancreatitis and cholangitis with the use of early cholecystectomy particularly in high-risk surgical and elderly patients. Aims: We conducted this systematic review and meta-analysis of randomized controlled trials to compare the early cholecystectomy versus wait and watch strategy after ES. Methods: We searched Medline, Scopus, Web of Science, and Cochrane database for randomized controlled trials comparing the 2 strategies in the management of choledocholithiasis after ES. Our primary outcome of interest was difference in mortality. We evaluated several secondary outcomes including difference in development of acute pancreatitis, biliary colic and cholecystitis, cholangitis and recurrent jaundice, nonbiliary adverse events, and length of hospital stay. Risk ratios (RR) were calculated for categorical variables and difference in means was calculated for continuous variables. These were pooled using random effects model. Results: Seven studies with 916 patients (455 cholecystectomy group and 461 wait and watch group) were included in the meta-analysis. Pooled RR with 95% confidence interval for mortality was 1.43 (0.93- 2.18), I2=9%. In the high-risk patient group, pooled RR was 1.39 (0.64-3.03) and in low-risk population pooled RR was 1.53 (0.79-2.96). Pooled RR for acute pancreatitis was 1.64 (0.46-5.81) with no heterogeneity. There was no difference in the rate of acute pancreatitis patients based on high-risk versus low-risk patients. Pooled RR for occurrence of biliary colic and cholecystitis during follow-up was 9.82 (4.27-22.59), I2=0%. Pooled RR for cholangitis and recurrent jaundice was 2.16 (1.14-4.07), I2=0%. However, there was no difference in the rate of cholangitis between the 2 groups in low-risk patients. Length of stay was shorter in the wait and watch group with a pooled mean difference was ?2.70 (?4.71, ?0.70) with substantial heterogeneity. Conclusions: Although we found no difference in mortality between the 2 strategies after ES, laparoscopic cholecystectomy should be recommended as it is associated with lower rates of subsequent recurrent cholecystitis, cholangitis, and biliary colic down the road even in high-risk surgical patients.