Background: Adjuvant mFFX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is a standard-of-care for fit patients (pts) with resected PDAC, owing to the immediate practice-changing PRODIGE 24/CCTG PA6 trial (2018). Five-year follow-up: median overall survival (mOS) 53.3 months (m) and median disease-free survival (mDFS) 21.4 m for mFFX vs 35.5 m and 12.8 m for gemcitabine (Conroy, JAMA Onc, 2022). RWO for pts outside a clinical trial are lacking. Herein, we report RWO for pts with resected PDAC and intent for adjuvant mFFX at Memorial Sloan Kettering (MSK). Methods: Institutional databases were queried to identify pts with resected PDAC who received any dose of adjuvant mFFX. Demographic, clinicopathologic, genomic, dosing details, and survival data were abstracted from medical and pharmacy records. Primary endpoint was to determine recurrence-free survival (RFS) calculated from start date mFFX to disease recurrence or death and OS calculated from start date mFFX to death. Secondary endpoints included dose reductions, significant treatment delay, toxicity profile, patterns of failure, genomic associations with outcome. RFS and OS are estimated using the Kaplan-Meier method. Study approved by MSK IRB. Results: N = 114 pts with resected PDAC treated with mFFX (> 1 dose) identified between 01/2015- 01/2022. Median age: 67 years (range 35 to 82); N = 43 (38%) > 70 years, N = 18 (16%) > 75 years, N = 2 (2%) > 80 years. Baseline Performance Status recorded in N = 104: N = 31 (30%) ECOG 0, N = 64 (62%) ECOG 1, N = 9 (9%) ECOG 2. Disease stage: N = 36 (32%) stage III, N = 61 (54%) stage II, and N = 17 (15%) pts stage I. Resection status: N = 91 (80%) R0, N = 23 (20%) R1. Presence of lymphovascular invasion: N = 92 (81%), perineural invasion N = 106 (93%). Median baseline CA 19-9: 20 U/mL (IQR; 9, 38). Median follow up: 22.4 m (range 6.2, 50.4). Median time from surgery to start mFFX: 7.4 weeks (IQR; 6.1, 9.3). Median # of mFFX doses received: 12 (IQR; 12, 12), N = 90 (79%) pts completed 12 doses. Dosing details available N = 112. N = 55 (49%) prescribed less than full dose of > one drug at baseline. Dose reductions: N = 57 (51%). N = 69 (62%) received < 12 doses oxaliplatin. N = 97 (87%) received growth factor support. mRFS: 31 m (95% CI; 23, Not Reached). N = 18 (16%) were hospitalized for treatment related adverse events, no therapy related mortality. N = 24 (21%) received adjuvant radiation therapy. One-year OS rate: 93% (95% CI; 89%, 98%) and 2-year OS rate: 78% (95%CI: 70%, 88%). Among patients with recurrence (N = 44), most common sites of first recurrence were: liver (N = 18, 41%), local (N = 14, 32%), and lung (N = 9, 20%). Conclusions: These data endorse mFFX as standard therapy for resected PDAC. The survival signals are encouraging in a prognostically unfavorable albeit select patient population (relative to PRODIGE 24). Dose adjustments to facilitate optimizing tolerability is key. Additional genomic and subtype analyses are underway.