Aims Atherosclerotic plaque characteristics play an important role in the development of coronary events. We investigated coronary plaque characteristics on multi-slice computed tomography (MSCT) and virtual histology intravascular ultrasound (VH IVUS) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD). Methods and results Fifty patients (25 with ACS, 25 with stable CAD) underwent 64-slice MSCT followed by VH IVUS in 48 (96%) patients. In ACS patients, 32% of plaques were non-calcified on MSCT and 59% were mixed [corresponding odds ratio (95% confidence intervals): 3.9 (1.6-9.5), P = 0.003 and 3.4 (1.6-6.9), P = 0.001, respectively]. In patients with stable CAD, completely calcified lesions were more prevalent (61%). On VH IVUS, the percentage of necrotic core was higher in the plaques of ACS patients (11.16 +/- 6.07 vs. 9.08 +/- 4.62% in stable CAD, P = 0.02). In addition, thin cap fibroatheroma was more prevalent in ACS patients (32 vs. 3% in patients with stable CAD, P = 0.001) and was most frequently observed in mixed plaques on MSCT. Plaque composition both on MSCT and VH IVUS was identical between culprit and non-culprit vessels of ACS patients. Conclusion On MSCT, differences in plaque characterization were demonstrated between patients with ACS and stable CAD. Plaques of ACS patients showed features of vulnerability to rupture on VH IVUS. Potentially, MSCT may be useful for non-invasive identification of atherosclerotic plaque patterns associated with higher risk.