Background: Pancreatic adenocarcinoma is a dreaded malignancy accounting for 7% of all cancer related deaths in the United States. The two most used chemotherapeutic regimens are a combination of 5- fluorouracil, leucovorin, oxaliplatin and irinotecan (FFX) and a combination of gemcitabine nab paclitaxel (GN). Both improve survival when compared to gemcitabine alone but have not been compared directly. Methods: Retrospective chart review of 83 chemotherapy naïve patients with metastatic cancer of exocrine pancreas who underwent chemotherapy between February 2011 and June 2017. Patients who completed at least one cycle of chemotherapy regimen were included. Characteristics, efficacy and adverse events between the two regimens were compared using appropriate statistical analyses. Results: 83 patients met selection criteria. 39 patients received FFX and 44 received GN. Mean age of FFX and GN patients was 69.7 (SD 8.7) (Median 66) and 72.3 (SD 8.8) (Median 69) yrs respectively (p = 0.100). The proportion of patients with ECOG performance scale ≤1 receiving FFX vs. GN was 50.8% vs. 49.2% and > 2 receiving FFX vs. GN was 33.3% vs 66.7% (p = .286). Of the 23 patients > 75 yrs., 7 received FFX and 16 received GN (p = .086). Median overall survival was 10.1 months (95% CI: 5.4-18.7) in FFX and 7.2 months in GN (95% CI: 5.4-11.3) [p = 0.037]. Median survival based on site of tumor was 10.2 months (95% CI: 6.7-13.8) in head and 10.1 months (95% CI: 4.3-14.7) in body and tail tumors [p = 0.776]. Incidence of vomiting in FFX / GN was 94.1% / 73.7% (p =.027), vomiting requiring hospital admission was 55.9% / 21.1% (p = 0.003). Other events requiring admission included: diarrhea 31.4% / 17.9%; anemia 5.7% / 10.3%; thrombocytopenia 11.4% / 7.7%; febrile neutropenia 28.6% / 12.8% and acute kidney injury 25.7% / 15.4%; no statistically significant differences between groups. Conclusions: Patients treated with FFX had a longer survival in this retrospective review. FFX is associated with an increased incidence of vomiting requiring hospitalization. FFX remains a preferred regimen in treating patients with good performance status regardless of age.