Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high.