177 Background: Positive peritoneal cytology (PPC) in the setting of pancreatic cancer predicts a poor prognosis, such that it is considered metastatic disease in the American Joint Commission on Cancer staging guidelines. We re-evaluate the role of PPC, with particular attention to outcomes following neoadjuvant therapy. Methods: We retrospectively identified 185 patients from January 1, 2000 to present with the diagnosis of pancreatic adenocarcinoma who had undergone peritoneal washings with cytology at the time of planned resection. Data regarding demographics, tumor stage, intraoperative cytology, surgical and chemoradiation therapeutics, and clinicopathological outcomes were analyzed, with the primary endpoints being disease-free and overall survival (DFS and OS). Results: 20 patients (11%) had PPC at the time of planned resection; of these, 11 patients (55%) received neoadjuvant therapy prior to surgery. 165 patients (89%) had negative peritoneal cytology (NPC) at the time of planned resection; of these, 75 (45%) received neoadjuvant therapy prior to surgery. All patients proceeded with resection in the absence of visible metastatic disease. 42% of NPC reached 2-year survival compared to just 20% of patients with PPC. Overall, patients with PPC vs. NPC had significantly poorer DFS (p<0.0064) and OS (p<0.0135). When stratifying by neoadjuvant therapy, in those patients with stage II disease or higher who did not receive neoadjuvant therapy, multivariable CART analysis revealed that PPC predicted poorer DFS compared with NPC (p<0.004). However, among stage II or higher disease receiving neoadjuvant therapy, it failed to show a significant difference in DFS or OS between PPC and NPC. Conclusions: Overall, patients with positive peritoneal cytology are shown to have worse DFS and OS compared to patients with negative peritoneal cytology in pancreatic adenocarcinoma. However, after multivariable analysis, the prognostic significance of positive peritoneal cytology disappears in those patients with stage II and higher disease receiving neoadjuvant therapy.