Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. In recent years, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT on survival in patients with resected stage I-III pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was analyzed for patients with clinical stage I-III resected carcinoma of the pancreas who underwent NAT or surgery first +/- adjuvant therapy. Univariate statistics were used to compare characteristics between groups. Analysis of variance and Kaplan Meier analyses were used to compare median survival for each clinical stage of disease.Multivariate analyses were performed using a Cox proportional hazards model. Results: 16,122 patients who underwent NAT and 16,869 patients who underwent surgery-first were included. Patients who underwent NAT tended to be younger, covered by private insurance, have a higher median income, greater comorbidities, higher clinical stage disease, and undergo a whipple. Additionally, NAT patients had a greater number of positive regional lymph nodes (9 vs. 6, respectively), although a similar number of nodes retrieved, and higher pathological stage disease. In patients with clinical stage I disease, adjuvant therapy was associated with improved median survival than NAT and surgery-alone (24.8, 18.5, 17.9 months, p < 0.0001, respectively). However, in stage II, adjuvant and NAT offered similar median survival, which was improved over surgery-alone (20.5, 20.1, and 12.4 months, p < 0.0001, respectively). In stage III, NAT had improved median survival than the other groups (19.6, 14.2, 8.6 months, p < 0.0001, respectively). In the multivariate survival analysis, patients who received NAT had a 22% lower hazard of mortality up to 5 years as compared to adjuvant therapy (p < 0.0001). Conclusions: Neoadjuvant therapy in advanced stage pancreatic cancer confers a survival benefit and may allow more patients to undergo surgery; NAT appears to offer similar survival as adjuvant therapy in early stage pancreatic cancer.