Background and aims <p>Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used for resecting large, laterally spreading colorectal polyps. While ESD offers higher <i>en bloc</i> resection rates, its comparative efficacy and safety relative to EMR remain uncertain, particularly in Western practice. This systematic review and meta-analysis aimed to evaluate the recurrence and adverse event rates of EMR versus ESD in adult patients with colorectal polyps  ≥ 20&#xa0;mm.</p> Methods <p>We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing EMR and ESD for colorectal polyps. Ovid MEDLINE and Embase were searched from inception to April 2024. The primary outcome was recurrence rate; secondary outcomes included total adverse events, bleeding, and perforation. Certainty of evidence was assessed using the GRADE framework.</p> Results <p>In this meta-analysis of three randomized controlled trials including 484 patients, ESD was associated with significantly lower recurrence rates compared to EMR (OR 3.24, 95% CI: 1.58–6.64), with high certainty of evidence. There were no significant differences between EMR and ESD in total adverse events (OR 0.96, 95% CI: 0.43–2.17), bleeding (OR 0.96, 95% CI: 0.41–2.27), or perforation rates (OR 0.96, 95% CI: 0.14–6.65), though certainty for these outcomes was moderate due to heterogeneity and imprecision.</p> Conclusion <p>ESD is associated with significantly lower recurrence rates compared to EMR in the treatment of large colorectal polyps, with high-certainty evidence. These findings support the use of ESD when recurrence risk is a primary concern, while EMR remains a feasible alternative with comparable safety.</p> PROSPERO <p>CRD420251048732.</p> Graphical abstract <p></p>