Background Cardiovascular diseases are a significant health burden with the prevalence increasing worldwide. Thus, a highly accurate assessment and prediction of death risk are crucial to meet the clinical demand. This study sought to develop and validate a model to predict in‐hospital mortality among patients with the acute coronary syndrome (ACS) using nonlinear algorithms. Methods A total of 2414 ACS patients were enrolled in this study. All samples were divided into five groups for cross‐validation. The logistic regression (LR) model and XGboost model were applied to predict in‐hospital mortality. The results of two models were compared between the variable set by the global registry of acute coronary events (GRACE) score and the selected variable set. Results The in‐hospital mortality rate was 3.5% in the dataset. Model performance on the selected variable set was better than that on GRACE variables: a 3% increase in area under the receiver operating characteristic (ROC) curve (AUC) for LR and 1.3% for XGBoost. The AUC of XGBoost is 0.913 (95% confidence interval [CI]: 0.910–0.916), demonstrating a better discrimination ability than LR (AUC = 0.904, 95% CI: 0.902–0.905) on the selected variable set. Almost perfect calibration was found in XGBoost (slope of predicted to observed events, 1.08; intercept, −0.103; p < .001). Conclusions XGboost modeling, an advanced machine learning algorithm, identifies new variables and provides high accuracy for the prediction of in‐hospital mortality in ACS patients.

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