377 Background: While small sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed given their indolent behavior, small bowel NETs are routinely resected with a regional lymphadenectomy regardless of size given their malignant potential. Considering this variability, our aim was to define the natural history of duodenal (D-NETs) and determine the role of resection. Secondary aim was to define clinicopathologic factors associated with overall survival (OS) in pts who undergo resection. Methods: All pts in the National Cancer Database (2004-14) diagnosed with non-metastatic, non-functional D-NETs were included. Local resection (LR) was defined as local excision, polypectomy, or excisional biopsy. Anatomic resection (AR) was defined as removal with radical surgery. Tumor size was divided into three categories (< 1 cm, 1-2 cm, ≥ 2 cm). Propensity score weighting analysis was used to create balanced cohorts between resection and no-resection pts; this was maintained in all three size categories. Primary endpoint was OS. Results: Among 5,502 pts, median age was 65 yrs; 52% were male. Median f/u was 51 mos. Median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954) of which 61% were LR and 39% were AR. At least one lymph node (LN) was retrieved in 25% of pts, of which 44% had LN metastasis. 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age, gender, race, Charlson-Deyo score, and tumor grade, all of which were independently associated with OS on MV Cox regression analysis, thus creating balanced cohorts. Resection was associated with improved median OS compared to no-resection (MNR vs 94 mos, p < 0.01); this persisted for all three size categories (< 1 cm: MNR vs 194 mos; 1-2 cm: MNR vs 56 mos; > 2 cm: MNR vs 90 mos; all p < 0.01). Subset analysis of each size cohort who underwent resection showed that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all p > 0.05). Conclusions: All pts with non-metastatic non-functional D-NETs should be considered for resection regardless of tumor size. Given their lack of prognostic value, the type of resection and extent of LN retrieval should be tailored to the patient’s clinical picture and safety profile.