BACKGROUND Non-invasive coronary angiography by multislice spiral computed tomography (MSCT) is a promising method for the diagnosis of coronary artery disease (CAD). However, the clinical role of this method has not been established for specific patient cohorts. Therefore, the objective of the current prospective, blinded study was to investigate the diagnostic value of coronary MSCT angiography in patients with an intermediate pre-test probability for having CAD when compared with invasive angiography. RESULTS A total of 243 patients with an intermediate pre-test probability for having CAD were asked to undergo coronary 16- or 64-slice CT angiography before planned invasive angiography from 12 September 2003 to 13 July 2005. The primary end point was defined as the diagnostic accuracy in the detection of significant coronary stenosis (> or =50% lumen diameter reduction) on a per-patient and an 'intention-to-diagnose'-based analysis. Secondary end points comprised per-artery and per segment-based analyses as well as the comparison of diagnostic accuracy of 16- vs. 64-slice MSCT angiography. Of 243 enrolled patients, 129 and 114 patients were studied by 16- and 64-slice CT angiography, respectively. The overall sensitivity, negative predictive value, and specificity for CAD detection by MSCT were 99% (95% CI, 94-99%), 99% (95% CI, 94-99%), and 75% (95% CI, 67-82%), respectively. On a per-segment basis, the use of 64-slice CT was associated with significantly less inconclusive segments (7.4 vs. 11.3%, P < 0.01), resulting in a trend to an improved specificity (92 vs. 88%, P = 0.09). CONCLUSIONS In patients with an intermediate pre-test probability for having CAD this large, prospective trial demonstrates that non-invasive coronary CT angiography is a very sensitive method for CAD detection. Furthermore, this method allows ruling out CAD very reliably and safely. Finally, 64-slice CT appears to be superior for CAD detection when compared with 16-slice CT.