OBJECTIVES: To compare the cost-effectiveness of FOLFIRINOX with nab-Paclitaxel plus Gemcitabine as first-line treatment for metastatic pancreatic cancer (MPC). METHODS: A Markov model was developed to simulate a cohort of patients with MPC to estimate the cost per life-year gained (LYG) and per quality-adjusted life-year (QALY) gained when treating with FOL versus nab-PAC-GEM from a societal perspective. Three health states were included in the model: stable disease, progressive disease, and death. The cohorts were modeled over a 3-year time horizon in a one-month cycle length. Efficacy data were obtained from phase 3 trial data in each regimen. All costs were measured in 2015 US dollars. Drug acquisition costs were based on prices from the Veteran Affairs Federal Supply Schedule. Procedure and physician-visit costs were derived from the Medicare physician-fee-schedule. Literature was used to estimate the adverse events costs and the utility scores for each health state. One-way sensitivity analyses were performed to determine the robustness of the model to changes in key parameters. RESULTS: The model projected a life expectancy of 9 months and 7 months for FOL and nab-PAC-GEM, respectively. The FOL group showed a higher QALY than the nab-PAC-GEM group (0.51 vs. 0.40). Although the drug acquisition costs were significantly lower in FOL compared with nab-Pac-Gem, FOL yielded a slightly higher cost after the 3-year period ($55,944 vs. $56,628). FOL treatment incurred an incremental cost of $1,334 per additional life-month ($16,012 per life-year) and an incremental cost of $30,870 per QALY gained. The median overall survival and progression-free survival point estimate greatly influenced model results based on the results of sensitivity analysis. CONCLUSIONS: Compared with nab-paclitaxel-gemcitabine, FOLFIRINOX showed a slightly higher cost but higher life expectancy and QALY as a first-line treatment in metastatic pancreatic cancer.  Using a U.S. willingness-to-pay threshold of $150,000 per QALY FOLFIRINOX was clearly cost-effective compared to nab-PAC-GEM.