Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. Recently, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT in resected pancreatic cancer. Methods: Patients with clinically staged I-III resected carcinoma of the pancreas who underwent at least NAT or surgery first in the 2003-2011 National Cancer Data Base were included. Univariate statistics were used to compare characteristics between treatment groups. Kaplan-Meier and multivariate survival analyses using Cox proportional hazards models were also performed. Results: 1736 patients who underwent NAT, 6706 patients who underwent surgical resection alone, and 9890 patients who underwent surgical resection followed by adjuvant therapy were studied. In patients with clinical stage I disease, adjuvant therapy was associated with similar median survival to NAT, which was greater than surgery alone (24.9, 24.8, and 18.3 months, respectively, p < 0.0001). However, in stage II, NAT offered improved median survival over adjuvant therapy, which was greater than surgery alone (21.78, 20.63, and 12.1 months, respectively, p < 0.0001). In stage III disease, NAT had better median survival relative to other groups (22.6, 14.6, and 8.7 months, respectively, p < 0.0001). In multivariate survival analysis, patients who received NAT had a 33% lower hazard of mortality up to 5 years as compared to surgical resection alone (p < 0.0001). Conclusion: Neoadjuvant therapy in advanced stage pancreatic cancer is associated with a survival benefit, perhaps related to a selection bias. In early stage pancreatic cancer, NAT is associated with similar survival. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.