Background Previous case series report that neuroendocrine tumors (NETs) of the ampulla of Vater have worse overall survival (OS) than NETs in the duodenum. We aimed to compare the OS of patients with ampullary NETs to patients with duodenal NETs. Methods This retrospective comparative cohort study used the Surveillance, Epidemiology, and End Results (SEER) registry from 1988 to 2009. OS was evaluated using Kaplan–Meier estimates and Cox proportional hazard regression. Results Ampullary NETs ( n  = 120) were larger (median size 18 vs. 10 mm, p  < 0.001), higher grade (poorly and undifferentiated tumor 42 % vs. 12 %, p  < 0.001), higher SEER historic stage (distant metastasis 16 % vs. 7 %, p  < 0.001), and more often resected (78 % vs. 60 %, p  < 0.001) than duodenal NETs ( n  = 1,360). Median OS was significantly worse for patients with ampullary NETs than with duodenal NETs (98 vs. 143 months, p  = 0.037). Local resection was performed for 50.5 % of the resected ampullary NETs and resulted in similar OS compared to locally resected duodenal NETs (HR 1.37, 95 % CI 0.76–2.48, p  = 0.291). Conclusions While ampullary NETs are more advanced at presentation and have worse OS than duodenal NETs, long-term survival is possible with proximal small bowel NETs. For locally resected NETs, OS is similar between ampullary and duodenal NETs.