Background: Surgical resection is the only potentially curative option for pancreatic cancer (PC). Unfortunately, just 15-20% of patients (pts) have resectable disease at the time of diagnosis. Recently, for a variety of reasons, neoadjuvant chemotherapy (NAC) has been widely adopted in both borderline resectable and resectable tumors. Most guidelines recommend either modified FOLFIRINOX (mFOLFIRINOX) or gemcitabine and NAB-paclitaxel (GnP) in this setting. This is largely based on phase II trials and extrapolations from trials in the metastatic setting. Here we investigate the difference in tumor regression score (TRS) and clinical outcomes between these regimens. Methods: We retrospectively collected data from pts who underwent resection of PC after NAC at Ochsner Health between July 2012 and July 2021. Primary objective was TRS on operative pathology as assessed by the reading pathologist. Secondary objectives were progression free survival (PFS) from the date of surgery and overall survival (OS) from the date of diagnosis. TRSs were dichotomized as complete (0)/moderate (1) responses versus (vs) minimal (2)/poor (3) responses. The dichotomized score was assessed using log-binomial regression. Kaplan-Meier survival analysis was utilized to estimate PFS and OS. Survival curves were compared by the log-rank test. Results: We identified 96 pts with PC who had NAC followed by surgical resection. Mean age at diagnosis was 65.7. 55% had borderline resectable and 45% had clearly resectable disease at diagnosis. 74 pts received mFOLFIRINOX and 22 pts received GnP. Pts receiving GnP were more likely to be older (71 vs 64, P = 0.001) and have a worse Eastern Cooperative Oncology Group performance status (PS) (P = 0.019). TRSs were similar between the 2 groups with 58.1% and 59.1% in each group achieving a TRS of 2. 7 pts in the mFOLFIRINOX group had TRS of 0 (CR) while 0 pts in the GnP group had a TRS of 0. When controlling for age and PS, risk ratio for a lower TRS (0/1 vs 2/3) with mFOLFIRINOX vs GnP was 1.22 (0.27 - 5.47). 40% and 36.4% had disease recurrence after mFOLFIRINOX and GnP, respectively. Median PFS and OS were 15.6 and 23.4 months (m) in the mFOLFIRINOX group and 18.9 and 27.6 m in the GnP group (P = 0.996, P = 0.933, respectively). On multivariate analysis, controlling for age and PS, hazard ratios for OS and PFS with mFOLFIRINOX vs GnP were 0.86 (95% CI 0.38–2.18) and 1.17 (95% CI 0.53–2.84), respectively. Conclusions: Our study showed no difference in TRS between mFOLFIRINOX or GnP as NAC, although the small number of pts who received GnP precluded statistical inference. Differences in survival outcomes between the two NAC regimens were not significantly different, and outcomes were comparable to those reported in the phase II SWOG S1505 trial. Large prospective trials comparing these two regimens in terms of efficacy and toxicity will be required to better answer these questions.