AIMS: Although some scores based on traditional statistical methods are available for risk stratification in patients hospitalized in cardiac intensive care units (CICUs), the interest of machine learning (ML) methods for risk stratification in this field is not well established. We aimed to build an ML model to predict in-hospital major adverse events (MAE) in patients hospitalized in CICU. METHODS AND RESULTS: In April 2021, a French national prospective multicentre study involving 39 centres included all consecutive patients admitted to CICU. The primary outcome was in-hospital MAE, including death, resuscitated cardiac arrest, or cardiogenic shock. Using 31 randomly assigned centres as an index cohort (divided into training and testing sets), several ML models were evaluated to predict in-hospital MAE. The eight remaining centres were used as an external validation cohort. Among 1499 consecutive patients included (aged 64 ± 15 years, 70% male), 67 had in-hospital MAE (4.3%). Out of 28 clinical, biological, ECG, and echocardiographic variables, seven were selected to predict MAE in the training set ( CONCLUSION: This new ML score is the first to demonstrate improved performance in predicting in-hospital outcomes over existing scores in patients admitted to the intensive care unit based on seven simple and rapid clinical and echocardiographic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.