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BACKGROUND: Coronary artery disease (CAD) results in substantial morbidity and mortality.OBJECTIVES: The purpose of this study was to develop a deep learning model to detect CAD defined using diagnostic codes ("ECG2CAD") and identify people at risk for adverse events using electrocardiograms (ECGs) in a primary care setting.METHODS: ECG2CAD was trained on 764,670 ECGs representing 137,199 individuals at Massachusetts General Hospital (MGH). Model performance for discrimination of prevalent CAD was measured using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), and compared against model of age and sex, and Pooled Cohort Equations, in 3 test sets: MGH, Brigham and Women's Hospital (BWH), and UK Biobank. Subgroups were assessed for incident CAD-related events in a BWH primary care cohort.RESULTS: ECG2CAD was evaluated in MGH (N = 18,706 [6,051 cases], age 57 ± 16 years), BWH (N = 88,270 [27,898 cases], age 57 ± 16 years), and UK Biobank (N = 42,147 [1,509 cases], age 65 ± 8 years). ECG2CAD consistently discriminated prevalent CAD (MGH AUROC: 0.782; AUPRC: 0.639; BWH: AUROC: 0.747; AUPRC: 0.588; UK Biobank AUROC: 0.760; AUPRC: 0.155) and incrementally vs models based on age and sex or Pooled Cohort Equations (P < 0.01) in MGH and BWH. In the BWH primary care subset, model performance was consistent across subgroups. Being in the highest quintile of ECG2CAD risk was associated with higher risk for adverse events compared with low-risk group (myocardial infarction HR: 5.59; 95% CI: 4.76-6.56, heart failure 10.49; 95% CI: 7.96-13.84, all-cause mortality 2.68; 95% CI: 2.32-3.10).CONCLUSIONS: Artificial intelligence-enabled analysis of the ECG may facilitate identification of individuals with possible undiagnosed CAD and inform downstream testing and preventive measures.