Background: Modifications to the FOLFIRINOX (FFX) regimen are used in the real world to attempt to decrease side effects and increase tolerability. This study assesses differences in healthcare resource utilization (HCRU) among patients who switched regimens following initial administration of first-line (1L) FFX among the Medicare fee-for-service (FFS) population with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: We identified patients aged 65+ with mPDAC between 2018-2021 in the Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Patients were required to have at least two malignant neoplasm of pancreatic duct diagnosis on different dates AND at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a FFX chemo infusion cycle: 1) FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-FU bolus and infusion), 2) FFX with no 5-FU bolus, but with 5-FU infusion, 3) FFX with a 5-FU bolus, but no 5-FU infusion, 4) FFX with no 5-FU of any kind and, 5) FFX with no leucovorin. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. The number of patients receiving FFX and the percentage of patients who switched cohorts (e. g. had a change in the FFX drug components received) at any time during the study was identified. HCRU differences were examined for patients at 60, 120, and 180 days after the initial administration for patients who did and did not switch cohorts. Results: We identified a total of 8,889 unique patients receiving 45,755 total administrations of 1L FFX. Cohort switching was observed in 16.7% of patients. Among patients receiving FFX with all 4 component drugs in the first cycle, 19% of subsequent administrations were different. Among patients who received modified FFX regimens, switching on subsequent regimens varied (7% for FFX with no 5-FU bolus, 47% for FFX with a 5-FU bolus but with no 5-FU infusion, 18% for FFX with no 5-FU of any kind, and 5% for FFX with no leucovorin). Inpatient costs were lower and hospital outpatient and growth factor costs were higher for patients who switched cohorts vs those that did not at 60 days, 120 days, and 180 days. Conclusions: One in six patients with mPDAC receiving first-line FFX switched component drugs at least once throughout the course of their treatment. These patients had higher hospital outpatient, higher growth factor, and lower inpatient costs compared to patients who did not switch. Over time, differences in inpatient costs between the two groups were sustained, while differences in hospital outpatient and growth factor exacerbated.