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Cardiovascular disease is the leading cause of death worldwide so, early prediction and diagnosis of cardiovascular disease is essential for patients affected by this fatal disease. The goal of this article is to propose a machine learning–based 1-year mortality prediction model after discharge in clinical patients with acute coronary syndrome. We used the Korea Acute Myocardial Infarction Registry data set, a cardiovascular disease database registered in 52 hospitals in Korea for 1 November 2005–30 January 2008 and selected 10,813 subjects with 1-year follow-up traceability. The ranges of hyperparameters to find the best prediction model were selected from four different machine learning models. Then, we generated each machine learning–based mortality prediction model with hyperparameters completed the range fitness via grid search using training data and was evaluated by fourfold stratified cross-validation. The best prediction model with the highest performance was found, and its hyperparameters were extracted. Finally, we compared the performance of machine learning–based mortality prediction models with GRACE in area under the receiver operating characteristic curve, precision, recall, accuracy, and F -score. The area under the receiver operating characteristic curve in applied machine learning algorithms was averagely improved up to 0.08 than in GRACE, and their major prognostic factors were different. This implementation would be beneficial for prediction and early detection of major adverse cardiovascular events in acute coronary syndrome patients. [ABSTRACT FROM AUTHOR]