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Endothelial Dysfunction is achieving increasing importance, because it is strictly related to cardiovascular risks and it provides important prognostic data in addition to the classical ones. This paper introduces a machine learning approach for predicting Endothelial Dysfunction. The approach was applied and tested on a newly collected dataset, “Endothelial Dysfunction Dataset (EDD)” and several machine learning algorithms are compared. This method comprises features related to the anthropometric or pathological characteristics of the analysed subjects. The experiments yield high accuracy, demonstrating the effectiveness and suitability of the proposed approach.