In this study, the ability of radiomics features extracted from myocardial perfusion imaging with SPECT (MPI-SPECT) was investigated for the prediction of ejection fraction (EF) post-percutaneous coronary intervention (PCI) treatment. A total of 52 patients who had undergone pre-PCI MPI-SPECT were enrolled in this study. After normalization of the images, features were extracted from the left ventricle, initially automatically segmented by k-means and active contour methods, and finally edited and approved by an expert radiologist. More than 1700 2D and 3D radiomics features were extracted from each patient’s scan. A cross-combination of three feature selections and seven classifier methods was implemented. Three classes of no or dis-improvement (class 1), improved EF from 0 to 5% (class 2), and improved EF over 5% (class 3) were predicted by using tenfold cross-validation. Lastly, the models were evaluated based on accuracy, AUC, sensitivity, specificity, precision, and F-score. Neighborhood component analysis (NCA) selected the most predictive feature signatures, including Gabor, first-order, and NGTDM features. Among the classifiers, the best performance was achieved by the fine KNN classifier, which yielded mean accuracy, AUC, sensitivity, specificity, precision, and F-score of 0.84, 0.83, 0.75, 0.87, 0.78, and 0.76, respectively, in 100 iterations of classification, within the 52 patients with 10-fold cross-validation. The MPI-SPECT-based radiomic features are well suited for predicting post-revascularization EF and therefore provide a helpful approach for deciding on the most appropriate treatment.