Background: The common first-line therapies for metastatic adenocarcinoma of the pancreas (mPC) are FOLFIRINOX and gemcitabine plus nab-paclitaxel (Gem-Nab-P). However, these treatments have not been directly compared in a clinical trial and comparative real-world data analyses on their effectiveness are limited. Using real-world data, we evaluated the impact on overall survival and post-treatment hospitalizations of 1L FOLFIRINOX vs. Gem-Nab-P in individuals with mPC. Methods: We performed a retrospective cohort study of 1L treatment of patients with mPC between 1/2015 and 6/2020, utilizing administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Inverse probability of treatment weighting (IPTW) was used to adjust for age, ECOG, Socioeconomic index (SDI), comorbidity, metastatic sites and pre-treatment. Median rwOS was estimated using the weighted Kaplan-Meier method. Results: Our cohort included 1,102 1L mPC patients, 566 (51.4%) treated with FOLFIRINOX (F), and 536 (48.6%) treated with Gem-Nab-P (GNP). F-treated patients were generally younger, with better performance status (ECOG PS), fewer comorbidities and living in regions with higher socioeconomic index. Following adjustments, the Median rwOS was 9.28 and 6.82 months for F-initiated patients and GNP, respectively (p-value = 2.5e-07). This survival benefit of F was observed among all sub-groups, including different ECOG PS, ages, socioeconomic index and metastatic sites. F-treated patients also had fewer post-treatment hospitalizations (p-value=0.027) and lower post-treatment costs (p-value=0.00004). Conclusions: Our retrospective cohort study demonstrated that FOLFIRINOX is associated with improved survival of approximately 2 months over Gem-Nab-P and is also associated with fewer post-treatments complications. A randomized controlled trial comparing these first line treatments is warranted to test the survival and post-treatment complications benefit of FOLFIRINOX over Gem-Nab-P.