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OBJECTIVE We aimed to develop a data-driven machine learning model for predicting critical deterioration events from routinely collected EHR data in hospitalized children. MATERIALS This retrospective cohort study included all pediatric inpatients hospitalized on a medical or surgical ward between 2014-2018 at a quaternary children's hospital. METHODS We developed a large data-driven approach and evaluated three machine learning models to predict pediatric critical deterioration events. We evaluated the models using a nested, stratified 10-fold cross-validation. The evaluation metrics included C-statistic, sensitivity, and positive predictive value. We also compared the machine learning models with patients identified as high-risk Watchers by bedside clinicians. RESULTS The study included 57,233 inpatient admissions from 34,976 unique patients. 3,943 variables were identified from the EHR data. The XGBoost model performed best (C-statistic=0.951, CI: 0.946 ∼ 0.956). CONCLUSIONS Our data-driven machine learning models accurately predicted patient deterioration. Future sociotechnical analysis will inform deployment within the clinical setting.