Abstract This study aimed to develop a predictive model integrating clinical, radiomics, and deep learning (DL) features of hyperattenuated imaging markers (HIM) from computed tomography scans immediately following mechanical thrombectomy (MT) to predict hemorrhagic transformation (HT). A total of 239 patients with HIM who underwent MT were enrolled, with 191 patients (80%) in the training cohort and 48 patients (20%) in the validation cohort. Additionally, the model was tested on an internal prospective cohort of 49 patients. A total of 1834 radiomics features and 2048 DL features were extracted from HIM images. Statistical methods, such as analysis of variance, Pearson’s correlation coefficient, principal component analysis, and least absolute shrinkage and selection operator, were used to select the most significant features. A K-Nearest Neighbor classifier was employed to develop a combined model integrating clinical, radiomics, and DL features for HT prediction. Model performance was evaluated using metrics such as accuracy, sensitivity, specificity, receiver operating characteristic curves, and area under curve (AUC). In the training, validation, and test cohorts, the combined model achieved AUCs of 0.926, 0.923, and 0.887, respectively, outperforming other models, including clinical, radiomics, and DL models, as well as hybrid models combining subsets of features (Clinical + Radiomics, DL + Radiomics, and Clinical + DL) in predicting HT. The combined model, which integrates clinical, radiomics, and DL features derived from HIM, demonstrated efficacy in noninvasively predicting HT. These findings suggest its potential utility in guiding clinical decision-making for patients with MT.