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Objective Patients with suspected acute aortic syndromes (AAS) often undergo CT with negative results. We sought clinical and diagnostic criteria to identify low risk patients, an initial step in developing a clinical decision rule. Methods We retrospectively identified all adults presenting to our Emergency Department (ED) from 1/1/2006- 8/1/2010 who underwent CT angiography for suspected AAS without prior trauma or AAS. 1,465 patients met inclusion criteria; a retrospective case-controlled review (ratio 1:4) was conducted. Cases were diagnosed with aortic dissection, intramural hematoma, penetrating atherosclerotic ulcer or ruptured aneurysm. Results 2.7% (40/1,465) of patients who underwent CT had an AAS, 2 additional cases were diagnosed after admission [ED miss rate 5% (2/42)]. Patients with AAS were significantly older than controls (66 vs 59 yrs; p=.008). Risk factors included abnormal chest radiograph [sensitivity 79% (26/33), specificity 82% (113/137)] and acute chest pain [sensitivity 83% (29/35), specificity 71% (111/157)]. None of the 19 patients with resolved pain upon ED presentation had AAS. These data support a two-step rule: first screen for ongoing pain; if present, screen for acute chest pain or an abnormal chest radiograph. This approach achieves a 54% (84/155) reduction in CT usage with a sensitivity for AAS of 96% (95% CI: 89%-100%), negative predictive value of 99.8% (99.4%-100%) and a false negative rate of 1.7% (1/84). Conclusions Our results demonstrate a need to safely identify patients at low risk for AAS who can forgo CT. We developed a preliminary two-step clinical decision rule, which requires validation.