Background: Significant variation exists in the management of potentially resectable pancreatic ductal adenocarcinoma (PDAC) across healthcare systems. We describe the results of a newly implemented neoadjuvant therapy pathway (NATP) in New York’s largest, most diverse health care system. Methods: The NATP was established in June 2019, consisting of a single-day pancreas multi-disciplinary clinic (PMDC) visit, followed by neoadjuvant therapy (NAT), imaging at specific intervals, and PMDC re-reviews at two and four months, prior to consideration of radiation and surgical resection. We conducted an IRB-approved retrospective analysis of patients enrolled in this pathway. Primary endpoints included completion of NATP and overall survival (OS). Results: The cohort consisted of 67 patients reviewed at PMDC and planned for NAT: 45% men, mean age 69.9 years, and 43% non-White between June 2019 and February 2022. Surgical stage at diagnosis was locally advanced (LAPC) 48%, borderline resectable (BRPC) 37% and resectable (RPC) 15%. Of 67 patients, 55 began the NATP (9 transferred care, and 3 declined NAT) and 28 (51%) completed NATP and underwent surgical exploration. Ten completed NATP and did not become surgical candidates, and 2 are still undergoing NAT. NATP was not completed in 15 patients due to 11 metastases (73.3%), 3 deaths (20%) and 1 local progression (6.7%) during NAT. NAT consisted of gemcitabine/nab-paclitaxel (GnP, 28%; 201 total cycles), FOLFIRINOX (45%; 251 total cycles), or a combination of both regimens (26%) with 31 (56%) patients receiving radiotherapy (97% SBRT). Of 28 patients who were explored, 86% underwent successful resection (62.5% R0, 16.7% R1 < 1mm and 20.8% R1). With median follow-up of 12.6 months, there were 17 deaths (31%) and median OS was reached at 20.9 mo (95% CI 10.5, 31.2); GnP vs. FOLFIRINOX median OS were 12.7 mo (95% CI 7.8, 17.6) vs. 26.1 mo (95% CI 9.3, 42.9) (p = 0.026). Median OS was not reached for the resected patients vs.16.3 months for non-resected (p = 0.006). Pathway adherence was seen in 28 (53%), with adherence improving median OS 20.9 mo vs. 16.3 mo (p = 0.039). NATP completion improved median OS 26.1 mo vs. 15.9 mo (p < 0.001). The percentage of patients that remained within the Northwell Health system for their post-NAT was higher among patients in the pathway, compared to prior (87% versus 44%). Conclusions: Implementation of NATP for pancreatic cancer within a single healthcare system increased the percentage of PDAC patients who underwent surgical resection and improved patient retention rate. Our data lay the foundation for further analysis of long-term outcomes of NAT in these patients.