Objective: This study investigated the correlation between positive resection margins and outcomes in patients with pancreatic ductal adenocarcinoma who underwent surgery and adjuvant chemotherapy according to the pivotal trial PRODIGE 24-CCTG PA-6. Background: The primary focus is on elucidating the prognostic significance of specific resection margins, including those associated with the superior-mesenteric vein (SMV), medial, and posterior pancreas. Methods: The analysis involved 400 patients across multiple centers in France and Canada. Surgical resection and subsequent adjuvant chemotherapy were core interventions. This study assessed the prognostic impact of resection margins, highlighting the significance of standardized pathology assessments. Additionally, the influence of chemotherapy regimen choice, comparing gemcitabine to mFOLFIRINOX, on the implications of positive resection margins was examined. Results: Only three margins, SMV (HR=1.48 95% CI [1.11;1.96], P <.001), medial (HR=1.92 95% CI [1.36;2.73], P <.001) and posterior (HR=1.65 95% CI [1.21;2.24], P =.002), had a significant prognostic impact on disease-free survival and were sufficient compared with the seven recommended margins (Kappa=0.90 95% CI [0.87; 0.94]). R1 status was significant independent prognostic factor for poorer survival in gemcitabine-treasted patients (HR=1.97 95% CI [1.23;3.16], P =.005) but lost its significance with mFOLFIRINOX (HR=1.46 95% CI [0.91;2.35], P =.114). Conclusions: All efforts should be made to evaluate the three margins of the highest prognostic value, with the others being secondary. A key finding of this study is the likely effect of mFOLFIRINOX on local invasion in operated patients, which seems to correct the impairment related to margin involvement, probably explaining the improvements in DFS and OS.