Endoscopic submucosal dissection (ESD) outperforms endoscopic papillectomy (EP) for ampullary tumors ≥20 mm in base size.

• ESD achieved 100% en bloc resection and 89.5% R0 rates compared to 71.7% and 30.2% for EP.
• ESD showed 0% residual disease versus 42.9% with EP during over a year of follow-up.

Consider ESD for better outcomes despite its technical demands, especially in larger tumors.

• Overall adverse event rates were similar: 36.8% for ESD and 22.6% for EP.