Introduction: Individualizing risk for stroke following a transient ischemic attack (TIA) is a topic of intense research, as existing scores are context-dependent or have not been well validated. The Canadian TIA Score stratifies risk of subsequent stroke into low, moderate and high risk. Our objective was to prospectively validate the Canadian TIA Score in a new cohort of emergency department (ED) patients. Methods: We conducted a prospective cohort study in 14 Canadian EDs over 4 years. We enrolled consecutive adult patients with an ED visit for TIA or nondisabling stroke. Treating physicians recorded standardized clinical variables onto data collection forms. Given the ability of prompt emergency carotid endarterectomy (CEA) to prevent stroke (NNT = 3) in high risk patients, our primary outcome was the composite of subsequent stroke or CEA ≤7 days. We conducted telephone follow-up using the validated Questionnaire for Verifying Stroke Free Status at 7 and 90 days. Outcomes were adjudicated by panels of 3 local stroke experts, blinded to the index ED data collection form. Based on prior work, we estimated a sample size of 5,004 patients including 93 subsequent strokes, would yield 95% confidence bands of +/− 10% for sensitivity and likelihood ratio (LR). Our analyses assessed interval LRs (iLR) with 95% CIs. Results: We prospectively enrolled 7,569 patients with mean 68.4 +/−14.7 years and 52.4% female, of whom 107 (1.4%) had a subsequent stroke and 74 (1.0%) CEA ≤7 days (total outcomes = 181). We enrolled 81.2% of eligible patients; missed patients were similar to enrolled. The Canadian TIA Score stratified the stroke/CEA ≤7days risk as: Low (probability <0.2%, iLR 0.20 [95%CI 0.091-0.44]; Moderate (probability 1.3%, iLR 0.79 [0.68-0.92]; High (probability 2.6%, iLR 2.2 [1.9-2.6]. Sensitivity analysis for just stroke ≤7 days yielded similar results: Low iLR 0.17 [95%CI 0.056-0.52], Medium iLR 0.89 [0.75-1.1], High iLR 2.0 [1.6-2.4]. Conclusion: The Canadian TIA Score accurately identifies TIA patients risk for stroke/CEA ≤7 days. Patients classified as low risk can be safely discharged following a careful ED assessment with elective follow-up. Patients at moderate risk can undergo additional testing in the ED, have antithrombotic therapy optimized, and be offered early stroke specialist follow-up. Patients at high risk should in most cases be fully investigated and managed ideally in consultation with a stroke specialist during their index ED visit.