Acute aortic syndrome (AAS) is a life threatening clinical syndrome resulting from three distinct diagnoses; acute aortic dissection, penetrating atherosclerotic ulcer and intramural hematoma. There are no widely accepted guidelines that are both safe and efficient to guide the clinician on when to suspect AAS. Our aim was to assess the need for a clinical decision rule to help improve diagnosis of AAS. We conducted a diagnostic accuracy systematic review and meta-analysis, a historical case control study and historical cohort study. We found wide variation in practice with a perceived need by physicians for a clinical decision rule. In addition we found it feasible to risk stratify patients at risk for AAS by historical, clinical and laboratory features. Therefore we conclude there is a need for the development of a clinical decision rule for the risk stratification of patients with a clinical suspicion of AAS.