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Background Evaluation for ischemia is appropriate in patients at risk for or with a history of coronary artery disease presenting with syncope. The aim of this study is to determine the prognostic value of stress echocardiography in patients presenting with syncope. Methods We examined our database of all patients undergoing stress echocardiography at our institution. Patients referred due to syncope were grouped as high risk based on any of the following: (1) known history of coronary artery disease, (2) left ventricular ejection fraction <50%, (3) moderate or severe mitral or aortic valve regurgitation, and (4) moderate mitral or aortic valve stenosis. The main outcomes were the presence of ischemia on stress imaging and all-cause mortality using the social security death index. Results A total of 225 patients were identified; mean age was 64.3 ± 14.5 years, the mean follow-up duration was 29.2 ± 13.8 months. There were 163 patients in the low-risk group and 62 patients in the high-risk group. On imaging, 7% of the overall cohort had ischemia. The low-risk group had 5 (3%) patients with ischemia and the high-risk group had 10 patients (16%) with ischemia (P < 0.01). The mortality rate was significantly higher in the high-risk group (3.99%/year vs. 1.02%/year; P = 0.02); this difference was not affected by the presence of ischemia. Conclusions High-risk patients with syncope as defined by appropriateness criteria and existing evidence carry a higher risk of ischemia and all-cause mortality. The presence of ischemia may not be predictive of long-term outcome in this group. [ABSTRACT FROM AUTHOR]