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Abstract Objective This study aims to compare the feasibility and effectiveness of automatic deep learning network and radiomics models in differentiating low tumor stroma ratio (TSR) from high TSR in pancreatic ductal adenocarcinoma (PDAC). Methods A retrospective analysis was conducted on a total of 207 PDAC patients from three centers (training cohort: n = 160; test cohort: n = 47). TSR was assessed on hematoxylin and eosin-stained specimens by experienced pathologists and divided as low TSR and high TSR. Deep learning and radiomics models were developed including ShuffulNetV2, Xception, MobileNetV3, ResNet18, support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), and logistic regression (LR). Additionally, the clinical models were constructed through univariate and multivariate logistic regression. Kaplan–Meier survival analysis and log-rank tests were conducted to compare the overall survival time between different TSR groups. Results To differentiate low TSR from high TSR, the deep learning models based on ShuffulNetV2, Xception, MobileNetV3, and ResNet18 achieved AUCs of 0.846, 0.924, 0.930, and 0.941, respectively, outperforming the radiomics models based on SVM, KNN, RF, and LR with AUCs of 0.739, 0.717, 0.763, and 0.756, respectively. Resnet 18 achieved the best predictive performance. The clinical model based on T stage alone performed worse than deep learning models and radiomics models. The survival analysis based on 142 of the 207 patients demonstrated that patients with low TSR had longer overall survival. Conclusions Deep learning models demonstrate feasibility and superiority over radiomics in differentiating TSR in PDAC. The tumor stroma ratio in the PDAC microenvironment plays a significant role in determining prognosis. Critical relevance statement The objective was to compare the feasibility and effectiveness of automatic deep learning networks and radiomics models in identifying the tumor-stroma ratio in pancreatic ductal adenocarcinoma. Our findings demonstrate deep learning models exhibited superior performance compared to traditional radiomics models. Key points • Deep learning demonstrates better performance than radiomics in differentiating tumor-stroma ratio in pancreatic ductal adenocarcinoma. • The tumor-stroma ratio in the pancreatic ductal adenocarcinoma microenvironment plays a protective role in prognosis. • Preoperative prediction of tumor-stroma ratio contributes to clinical decision-making and guiding precise medicine. Graphical Abstract |