Objectives: To develop and validate a risk score predicting arrhythmias for patients with syncope remaining unexplained after emergency department (ED) noninvasive evaluation. Methods: One cohort of 175 patients with unexplained syncope (Geneva, Switzerland) was used to develop and cross-validate the risk score; a second cohort of 269 similar patients (Pittsburgh, PA) was used to validate the system. Arrhythmias as a cause of syncope were diagnosed by cardiac monitoring or electrophysiologic testing. Data from the patient's history and 12-lead emergency electrocardiography (ECG) were used to identify predictors of arrhythmias. Logistic regression was used to identify predictors for the risk-score system. Risk-score performance was measured by comparing the proportions of patients with arrhythmias at various levels of the score and receiver operating characteristic (ROC) curves. Results: The prevalence of arrhythmic syncope was 17% in the derivation cohort and 18% in the validation cohort. Predictors of arrhythmias were abnormal ECG (odds ratio [OR]: 8.1, 95% confidence interval [CI] = 3.0 to 22.7), a history of congestive heart failure (OR: 5.3, 95% CI = 1.9 to 15.0), and age older than 65 (OR: 5.4, 95% CI = 1.1 to 26.0). In the derivation cohort, the risk of arrhythmias ranged from 0% (95% CI = 0 to 6) in patients with no risk factors to 6% (95% CI = 1 to 15) for patients with one risk factor, 41% (95% CI = 26 to 57) for patients with two risk factors, and 60% (95% CI = 32 to 84) for those with three risk factors. In the validation cohort, these proportions varied from 2% (95% CI = 0 to 7) with no risk factors to 17% (95% CI = 10 to 27) with one risk factor, 35% (95% CI = 24 to 46) with two risk factors, and 27% (95% CI = 6 to 61) with three risk factors. Areas under the ROC curves ranged from 0.88 (95% CI = 0.84 to 0.91) for the derivation cohort to 0.84 (95% CI = 0.77 to 0.91) after cross-validation within the same cohort and 0.75 (95% CI = 0.68 to 0.81) for the external validation cohort. Conclusions: In patients with unexplained syncope, a risk score based on clinical and ECG factors available in the ED identifies patients at risk for arrhythmias.