BackgroundThe incidence of duodenal adenocarcinoma is increasing, with limited studies on this disease published. This multicenter retrospective study aimed to analyze the clinicopathologic features of duodenal adenocarcinoma and identify prognostic factors for postoperative survival. MethodsDemographic characteristics, clinicopathologic features, treatment outcomes, and survival of patients with duodenal adenocarcinoma undergoing surgical treatment at 16 Chinese medical centers from 2012 to 2023 were retrospectively analyzed. ResultsAmong the 2,189 patients with duodenal adenocarcinoma included, 50.07% had extra-ampullary duodenal adenocarcinoma and 49.93% had peri-ampullary duodenal adenocarcinoma. The 1-, 3-, and 5-year overall survival rates for patients who underwent radical surgery were 91.78%, 69.30%, and 55.86%, respectively. The median overall survival was 73 months (range, 64–84), and the median progression-free survival was 64 months (range, 52–76). No differences in survival were observed between the laparotomy and minimally invasive surgery groups (log-rank P = .562); furthermore, no significant between-group differences in operation time, lymph node dissection, postoperative complications, or in-hospital mortality were observed (P > .05). The minimally invasive surgery group experienced less intraoperative blood loss (250 mL vs 100 mL, P < .001), fewer intraoperative blood transfusions (24.97% vs 18.84%, P = .002), and shorter hospital stays (28 days vs 23 days, P < .001). Multivariate Cox regression analysis revealed that advanced age, advanced stage, longer operation time, intraoperative blood transfusion, and postoperative hemorrhage were independent risk factors for poor prognosis. ConclusionRadical surgery was associated with favorable overall survival among patients with duodenal adenocarcinoma, and no difference in survival was observed between patients with extra-ampullary duodenal adenocarcinoma and peri-ampullary duodenal adenocarcinoma. Minimally invasive surgery is a reliable alternative for duodenal adenocarcinoma treatment.