Background and Aims Endoscopic sphincterotomy (ES) used to be part of sphincter of Oddi dysfunction (SOD) management, but recent studies changed attitudes about its utility. We conducted a systematic review and meta-analysis of randomized sham-controlled trials (RCTs) investigating ES for biliary SOD-related pain. Methods Articles were retrieved from PubMed, Medline, Embase, and CENTRAL. We included RCTs comparing ES with a sham procedure on post-cholecystectomy patients ≥18 years old with biliary SOD. Standardized data collection sheets were used, as well as the Risk of Bias 2 tool. A random-effects model was used to calculate risk ratios (RRs) with 95% confidence intervals (CIs). Subgroups included normal vs abnormal sphincter of Oddi manometry (SOM) and type II vs III SOD. Results From 517 articles retrieved, 4 RCTs were included, encompassing 376 patients. Overall, no difference existed between ES and the sham procedure in improving biliary SOD-related pain overall (RR 1.32, 95% CI 0.77-2.26, P = .31) and for the normal (RR 0.83, 95% CI 0.42-1.65, P = .60) and abnormal SOM subgroups (RR 1.90, 95% CI 0.84-4.29, P = .12). ES was numerically favored over the sham procedure in patients with type II (RR 2.51, 95% CI 1.32-4.81, P = .005) but not type III SOD (RR 1.02, 95% CI 0.32-3.27, P = .98). However, there was no significant subgroup difference between these type-based subgroups (P = .18, I2 = 43.2%). Conclusion ES does not improve biliary SOD-related pain overall or for type II vs III SOD or normal vs abnormal SOM subgroups. This meta-analysis confirms that there is no proven role for SOM or ES in managing SOD.