Early and accurate triage of patients with possible ischemic chest pain remains challenging in the emergency department because current risk stratification techniques have significant cost and limited availability. The aim of this study was to determine the diagnostic value of the coronary artery calcium score (CACS) for the detection of obstructive coronary artery disease (CAD) in low- to intermediate-risk patients evaluated in the emergency department for suspected acute coronary syndromes. A total of 225 patients presenting to the emergency department with acute chest pain and Thrombolysis In Myocardial Infarction (TIMI) scores <4 who underwent non-contrast- and contrast-enhanced coronary computed tomographic angiography were included. CACS was calculated from the noncontrast scan using the Agatston method. The prevalence of obstructive CAD (defined from the contrast scan as <50% maximal reduction in luminal diameter in any segment) was 9% and increased significantly with higher scores (p <0.01 for trend). CACS of 0 were observed in 133 patients (59%), of whom only 2 (1.5%) had obstructive CAD. The diagnostic accuracy of CACS to detect obstructive CAD was good, with an area under the receiver-operating characteristic curve of 0.88 and a negative predictive value of 99% for a CACS of 0. In a multivariate model, CACS was independently associated with obstructive CAD (odds ratio 7.01, p = 0.02) and provided additional diagnostic value over traditional CAD risk factors. In conclusion, CACS appears to be an effective initial tool for risk stratification of low- to intermediate-risk patients with possible acute coronary syndromes, on the basis of its high negative predictive value and additive diagnostic value.