Purpose: The diagnosis of acute aortic dissection (AoD) constitutes a major challenge. To assist physicians, the American Heart Association (AHA) has proposed a detection risk score based on high-risk predisposing conditions, pain features and physical examination. Such score identifies patients at low, intermediate and high risk of AoD. In the low-risk group, absence of a widened mediastinum on chest X-ray has been suggested as a mean to safely rule out AoD without further aortic imaging. However, the AHA risk score and derived diagnostic algorithm is awaiting validation. The aim of our study was to evaluate the diagnostic performance of the AoD AHA risk score in the emergency department (ED). Methods: Consecutive adult patients suspected of AoD from 2 EDs were included in a prospective registry from January 2008 to December 2012. Patients were classified according to the AHA risk score and the prevalence of AoD was calculated in each risk group. Furthermore, we estimated the prevalence of AoD in low-risk patients with a not-widened mediastinum on chest X-ray (CXR). The final diagnosis of AoD was obtained with computed tomography, angiography, surgery or autopsy. Results: Among the 1279 patients (mean age 68 years) included in the study, 236 (18.4%) were diagnosed with AoD; 365 (28.5%) patients presented at least one predisposing high-risk condition, 358 (27.9%) a high-risk pain feature and 342 (26.7%) a high-risk physical examination finding. 461 (36%) patients were classified as low-risk, 595 (46.5%) as intermediate-risk and 223 (17.4%) as high-risk. The respective prevalence of AoD was 10.1%, 18.9% and 34% in the 3 groups. Among the 420 (91%) low-risk patients with available CXR, the mediastinum was not-widened in 28 (60%) of 47 patients with AoD. Hence, 6.6% of low-risk patients with a not-widened mediastinum on CXR had AoD. Conclusion: The AHA risk score correctly stratifies patients for AoD prevalence in the ED. However AoD can not safely be rule out in the low risk patients even if a not-widened mediastinum is detected at CXR.