Introduction: Acute aortic syndrome (AAS) is a rare clinical syndrome with a high mortality encompassing acute aortic dissection, intramural hematoma and penetrating atherosclerotic ulcer. The objective of our study was to assess the diagnostic accuracy of high risk historical, examination and basic investigative features for AAS, in confirmed cases of AAS and a low risk control group in order to address the spectrum bias in previous diagnostic accuracy studies. Methods: We performed a historical matched case-control study: participants were adults >18 years old presenting to two tertiary care emergency departments (ED) or one regional cardiac referral center. Cases: new ED or in-hospital diagnosis of non-traumatic AAS confirmed by computed tomography or echocardiography. Controls: triage diagnosis of truncal pain (<14 days) and an absence of a clear diagnosis on basic investigation. Cases and controls were matched in a 4:1 ratio by sex and age. A sample size of 165 cases and 660 controls was calculated based on 80% power and confidence interval of 95% to detect an odds ratio of greater than 2. Results: Data were collected from 2002-2014 yielding 194 cases of AAS and 776 controls (mean age of 65(SD 14.1) and 66.7% male). Of the 194 cases of AAS, 32 (16.5%) were missed on initial assessment. Chest pain unspecified (20.7%), abdominal pain unspecified (9.9%) and acute coronary syndrome (8.7%) were the top diagnoses in the control population. Absence of acute onset pain (Sensitivity 95.9% negative likelihood ratio (LR-) 0.07(0.03-0.14)), and a negative D-dimer (Sensitivity 96.7%, LR- 0.05(0.01-0.18)) can help rule out AAS. Presence of tearing/ripping pain (Specificity 99.7%, LR+42.1 (9.9-177.5), a history of aortic aneurysm (Specificity 97.8%, LR+6.35(3.54-11.42)), hypotension (Specificity 98.7%, LR+ 17.2(8.8-33.6)), pulse deficit (Specificity 99.3, LR+31.1(11.2-86.6)), neurological deficits (Specificity 96.9%, LR+ 5.26(2.9-9.3)), and a new murmur (Specificity 97.8%, LR+ 9.4(5.5-16.2) ) can help rule in the diagnosis of AAS. Conclusion: Patients with one or more high-risk feature should be considered high risk, whereas patients with no high risk and multiple low risk features are at low risk for AAS. Further research should focus on a combination of these factors to guide who warrants further investigation thus reducing miss rate, morbidity and mortality.