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Background: Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently referred to tertiary centers after unsuccessful attempted resections at other institutions. The outcome of these patients who are ultimately resected is not well understood. Methods: We performed a retrospective review of patients with PDAC who underwent re-exploration between 1995 and 2013 at a single high volume tertiary care institution. We aimed to evaluate the association of neoadjuvant therapy prior to re-exploration on pathologic findings and clinical outcome in previously explored patients with PDAC. Results: Between 1995 and 2013, 50 of the 2,062 patients who were surgically explored underwent pancreatic resection following a previous exploration where they were deemed unresectable. The most common reason for unresectability at initial operation was vascular invasion (80%) and a presumed R2 resection. Thirty-seven (74%) patients received neoadjuvant therapy. Neoadjuvant therapy was associated with improved TNM stage (P=0.002), fewer positive lymph nodes (0 vs. 2, P=0.025), and improved median survival (24 vs. 13 months, P=0.044). Compared to R2 resected patients with PDAC who had not previously been explored, re-explored patients had significantly lower pathologic T and N stages (P<0.001) and a longer median survival (19 vs. 10 months, P<0.001). Conclusions: Patients with PDAC deemed unresectable may warrant re-exploration. Treatment with neoadjuvant therapy between operations is associated with improved pathological stage and survival. In this highly selected group of patients, successful resection is associated with improved survival compared to R2 resections.