e16244 Background: Transduodenal ampullectomy (TDA) has been attempted in early ampullary cancer. However, the indication and extent of TDA with curative intent remain controversial. Here, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent TDA. Methods: Ten early ampullary cancer patients who underwent TDA and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy (SSPPD) at this institute were respectively enrolled. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. Results: In terms of the perioperative outcomes between the TDA and SSPPD groups, the TDA group exhibited a shorter operating time (244 minutes vs. 390 minutes, p = 0.003), less intraoperative blood loss (67.5 grams vs. 774 grams, p = 0.006) and shorter length of postoperative hospital stay (15 days vs. 33 days). With respect to the postoperative nutrition status, the TDA group exhibited less postoperative weight loss (0.67% vs. 8.95%, p = 0.021), a better CONUT score (1.0 vs. 2.1, p = 0.011) and a better PNI score (42.9 vs. 40.9, p = 0.018). The 5-year survival rate in the adenoma with high-grade dysplasia (HGD) and T1a (M) groups was 100%, while the median survival time in the T1a (OD) group was 20.7 months (p = 0.0028). Conclusions: TDA is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with HGD or T1a (M) ampullary cancer.