Purpose <p>To develop and validate a magnetic resonance imaging (MRI)-based pancreatic risk stratification model (M-PRiSM) for prognosis prediction and therapy guidance in pancreatic ductal adenocarcinoma (PDAC).</p> Materials and methods <p>In this retrospective multicenter study, a total of 540 patients with PDAC were enrolled. A Cox proportional hazards model was used to identify significant clinical-radiological predictors and develop an M-PRiSM risk score system. The performance of the model was assessed using Harrell’s C-index, time-dependent area under the curve (AUC), and calibration curves, and was compared with existing clinical prediction metrics, including the 8^th American Joint Committee on Cancer (AJCC) staging and CA19-9 levels.</p> Results <p>540 PDAC patients were split into a development cohort (<i>n</i> = 282) and an internal validation cohort (<i>n</i> = 122), with 136 patients forming external cohort A (<i>n</i> = 80) and B (<i>n</i> = 56). The model, incorporating CA19-9 (hazard ratio (HR), 1.604, <i>p</i> = 0.047), margin (HR, 1.918, <i>p</i> = 0.001), tumor size (HR, 1.308, <i>p</i> = 0.003), and venous enhancement ratio (VER) (HR, 0.605, <i>p</i> = 0.047), was developed, showing superior predictive accuracy for OS with C-indexes of 0.73, 0.70, and 0.70, and 0.68 across four cohorts. The model outperformed the 8th AJCC staging and CA19-9 alone across validation cohorts (<i>p</i> &lt; 0.001). High-risk patients exhibit the worst overall survival (OS) and a higher frequency of adverse pathological features, but benefited significantly from adjuvant therapy, with improved survival outcomes.</p> Conclusion <p>The M-PRiSM model effectively predicts postoperative OS and identifies PDAC patients likely to benefit from adjuvant treatment.</p> Critical relevance statement <p>The M-PRiSM model, utilizing MRI and clinical features, enables preoperative risk stratification for overall survival in pancreatic ductal adenocarcinoma, offering a generalizable tool to guide personalized adjuvant therapy and enhance prognostic assessment.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>The M-PRiSM model can effectively predict pancreatic ductal adenocarcinoma survival.</p> </ItemContent> <ItemContent> <p>The M-PRiSM model showed strong generalizability in external validations.</p> </ItemContent> <ItemContent> <p>The M-PRiSM model stratifies patients for guiding adjuvant therapy for improved outcomes.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>