Objectives <p>To explore a novel approach for the early prediction of malignant cerebral edema (MCE) in stroke patients using radiomics features extracted from dual-energy computed tomography angiography (DE-CTA) reconstructed images of infarcted brain tissue.</p> Materials and methods <p>This retrospective study enrolled 398 stroke patients who underwent DE-CTA between April 2016 and November 2022 from three medical centers. Patients were allocated into a training cohort (<i>n</i> = 227) and a test cohort (<i>n</i> = 171) based on their source institution. Radiomics features were extracted from DE-CTA reconstructions of the infarct tissue. Radiomics models were built for each reconstruction scan images and for a combined model using features from all images. Additionally, a nomogram model integrating significant radiomics features and clinical characteristics was developed. The diagnostic performance of all models was evaluated using receiver operating characteristic (ROC) curve analysis, calculating the area under the curve (AUC).</p> Results <p>Radiomics models based on each individual DE-CTA reconstruction demonstrated robust predictive performance. In the test cohort, the combined radiomics model integrating features from all DE-CTA reconstructions significantly superior predictive performance compared to most single-image models. In the test cohort, both the combined radiomics model (AUC = 0.950) and the nomogram model (AUC = 0.935) significantly outperformed the clinical model (AUC = 0.574), both <i>p</i> &lt; 0.001. No significant difference in performance was observed between the nomogram and the radiomics model (<i>p</i> = 0.30).</p> Conclusions <p>Radiomics models derived from DE-CTA reconstructed images of infarcted tissue provide a reliable method for the early prediction of MCE development in stroke patients.</p>