Objective Patients with suspected acute aortic syndromes (AAS) often undergo computed tomography (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 January 1, 2006, to August 1, 2010, who underwent CT angiography for suspected AAS without prior trauma or AAS. A total of 1465 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 Of the patients who underwent CT, 2.7% (40/1465) 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 years; 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 2-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% confidence interval, 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 2-step clinical decision rule, which requires validation.