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Background: In-hospital cardiac arrest is a major burden to public health, which affects patient safety. Although traditional track-and-trigger systems are used to predict cardiac arrest early, they have limitations, with low sensitivity and high false-alarm rates. We propose a deep learning-based early warning system that shows higher performance than the existing track-and-trigger systems., Methods and Results: This retrospective cohort study reviewed patients who were admitted to 2 hospitals from June 2010 to July 2017. A total of 52 131 patients were included. Specifically, a recurrent neural network was trained using data from June 2010 to January 2017. The result was tested using the data from February to July 2017. The primary outcome was cardiac arrest, and the secondary outcome was death without attempted resuscitation. As comparative measures, we used the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPRC), and the net reclassification index. Furthermore, we evaluated sensitivity while varying the number of alarms. The deep learning-based early warning system (AUROC: 0.850; AUPRC: 0.044) significantly outperformed a modified early warning score (AUROC: 0.603; AUPRC: 0.003), a random forest algorithm (AUROC: 0.780; AUPRC: 0.014), and logistic regression (AUROC: 0.613; AUPRC: 0.007). Furthermore, the deep learning-based early warning system reduced the number of alarms by 82.2%, 13.5%, and 42.1% compared with the modified early warning system, random forest, and logistic regression, respectively, at the same sensitivity., Conclusions: An algorithm based on deep learning had high sensitivity and a low false-alarm rate for detection of patients with cardiac arrest in the multicenter study., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)