Introduction: The Canadian Syncope Risk Score (CSRS) was developed to identify patients at risk for serious adverse events (SAE) within 30 days of an Emergency Department (ED) visit for syncope. We sought to validate the score in a new cohort of ED patients. Methods: We conducted a multicenter prospective cohort study at 8 large academic tertiary-care EDs across Canada from March 2014 to Dec 2016. We enrolled adults (age 16 years) who presented within 24 hours of syncope, after excluding those with persistent altered mentation, witnessed seizure, intoxication, and major trauma requiring hospitalization. Treating ED physicians collected the nine CSRS predictors at the index visit. Adjudicated SAE included death, arrhythmias and non-arrhythmic SAE (myocardial infarction, serious structural heart disease, pulmonary embolism, severe hemorrhage and procedural interventions within 30-days). We assessed area under the Receiver Operating Characteristic (ROC) curve, score calibration, and the classification performance for the various risk categories. Results: Of the 2547 patients enrolled, 146 (5.7%) were lost to follow-up and 111 (4.3%) had serious condition during the index ED visit and were excluded. Among the 2290 analyzed, 79 patients (3.4%; 0.4% death, 1.4% arrhythmia) suffered 30-day serious outcomes after ED disposition. The accuracy of the CSRS remained high with area under the ROC curve at 0.87 (95%CI 0.82-0.92), similar to the derivation phase (0.87; 95%CI 0.84-0.89). The score showed excellent calibration at the prespecified risk strata. For the very-low risk category (0.3% SAE of which 0.2% were arrhythmia and no deaths) the sensitivity was 97.5% and negative predictive value was 99.7% (95%CI 98.7-99.9). For the very high-risk category (61.5% SAE of which 26.9% were arrhythmia and 11.5% death) the specificity was 99.4% and positive predictive value was 61.5% (95% CI 43.0-77.2). Conclusion: In this multicenter validation study, the CSRS accurately risk stratified ED patients with syncope for short-term serious outcomes after ED disposition. The score should aid in minimizing investigation and observation of very-low risk patients, and prioritization of inpatient vs outpatient investigations or following of the rest. The CSRS is ready for implementation studies examining ED management decisions, patient safety and health care resource utilization.