Data on the diagnostic accuracy of multislice computed tomographic coronary angiography (CTA) have been mostly derived from patients with a high pretest likelihood of coronary artery disease. Systematic comparisons with invasive angiography in patients with an intermediate pretest likelihood are scarce. The purpose of the present study was to determine the diagnostic accuracy of CTA in patients without known coronary artery disease with an intermediate pretest likelihood. A total of 61 patients (61% men, average age 57 ± 9 years) who had been referred for invasive coronary angiography underwent additional 64-slice CTA. A total of 920 segments were identified by invasive coronary angiography, of which 885 (96%) were interpretable on CTA. Invasive coronary angiography identified a significant stenosis (≥50% luminal narrowing) in 29 segments, of which 23 were detected on CTA. Thus, the sensitivity, specificity, positive predictive value, and negative predictive value was 79%, 98%, 61%, and 99%, respectively, for CTA. On a patient level, the sensitivity, specificity, positive predictive value, and negative predictive value was 100%, 89%, 76%, and 100%, respectively. CTA correctly ruled out the presence of significant stenosis in 40 (66%) of the 61 patients. In conclusion, the results from the present study have confirmed that CTA has excellent diagnostic accuracy in the target population of patients with an intermediate pretest likelihood. The high negative predictive value allowed us to rule out significant stenosis in a large proportion of patients. CTA can, therefore, be used as a highly effective gatekeeper for invasive coronary angiography.