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Purpose: To examine the prognostic significance of pretreatment 2-deoxy-2-[18F]fluoro-d-glucose ([18F]-FDG) positron emission tomography (PET)-based radiomic features using a machine learning approach in patients with endometrial cancers. Procedures: Included in this retrospective study were 53 patients with endometrial cancers who underwent [18F]-FDG PET/X-ray computed tomography (CT) before treatment. Since two different PET scanners were used, post-reconstruction harmonization was performed for all PET parameters using the ComBat harmonization method. Four clinical (age, histological type, stage, and treatment method) and 40 [18F]-FDG PET-based radiomic features were ranked, and a subset of useful features was selected based on the decrease in the Gini impurity in terms of associations with disease progression. The machine learning algorithms (random forest, neural network, k-nearest neighbors (kNN), naive Bayes, logistic regression, and support vector machine) were compared using the areas under the receiver operating characteristic curve (AUC) and validated by the random sampling method. Progression-free survival (PFS) and overall survival (OS) were assessed by the Cox regression analysis. Results: The five best predictors of disease progression were coarseness, gray-level run length nonuniformity, stage, treatment method, and gray-level zone length nonuniformity. The kNN model obtained the best performance classifier for predicting the disease progression (AUC =0.890, accuracy =0.849, F1 score =0.848, precision =0.857, and recall =0.849). Coarseness which was the first ranked radiomic feature was selected for survival analyses, and only coarseness remained as a significant and independent factor for both PFS (hazard ratios (HR), 0.65; 95 % confidence interval [CI], 0.49–0.86; p=0.003) and OS (HR, 0.52; 95 % CI, 0.36–0.76; p<0.001) at multivariate Cox regression analysis. Conclusions: [18F]-FDG PET-based radiomic analysis using a machine learning approach may be useful for predicting tumor progression and prognosis in patients with endometrial cancers. [ABSTRACT FROM AUTHOR]