Endoscopic retrograde cholangiopancreatography (ERCP) is a therapeutic procedure for skilled endoscopists that can be even more challenging in some situations, including patients' post-Roux-en-y Gastric Bypass (RYGB) surgery. There is still no consensus on whether laparoscopic-assisted ERCP (LA-ERCP) or endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) is the most appropriate, safe, and feasible approach in patients with this type of post-surgical anatomy. This systematic review and meta-analysis aimed to examine both approaches' feasibility, efficacy, and safety in this situation. We searched for electronic databases (MEDLINE, EMBASE, Lilacs, Google Scholar, and Central Cochrane) to identify studies comparing LA-ERCP versus EDGE. Outcomes measured included technical success, adverse events (AEs) and serious AEs, length of stay (LOS), and procedural time. Descriptive data related to the EDGE procedure was also extracted. The risk of bias and the quality of evidence of the enrolled studies were assessed. Five studies, totalizing 268 patients (176 LA-ERCP and 92 EDGE), were included. There was no statistical difference in technical success and AEs between groups; however, the LOS and procedural times were shorter for the EDGE group. High rates of fistula closure and no weight regain were observed in EDGE. Both methods are feasible and safe techniques to perform ERCP in patients with RYGB anatomy, with comparable technical success and adverse events rate. However, EDGE is associated with shorter LOS and procedural time.