Coronary plaque composition cannot be assessed accurately using gray-scale intravascular ultrasound (IVUS). Using virtual histology IVUS (VH-IVUS), a comparison of coronary plaque composition between acute coronary syndromes (ACS) and stable angina pectoris (SAP) was performed. Preintervention IVUS of de novo culprit and target lesions was performed in 318 patients (123 with ACS and 195 with SAP). Using VH-IVUS, plaque was characterized as fibrotic, fibrofatty, dense calcium, and necrotic core. VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was defined as necrotic core>or=10% of plaque area without overlying fibrous tissue in a plaque burden>or=40%. Lesions were classified into 3 groups: ruptured, VH-TCFA, and non-VH-TCFA plaque. Unstable lesions were defined as either VH-TCFA or ruptured plaque. Compared with patients with SAP, those with ACS had significantly more unstable lesions (89% vs 62%, p<0.001). Planar VH-IVUS analysis at the minimum luminal site and at the largest necrotic core site and volumetric analysis over a 10-mm-long segment centered at the minimum luminal site showed that the percentage of necrotic core was significantly greater and that the percentage of fibrofatty plaque was significantly smaller in patients with ACS. The percentages of fibrotic and fibrofatty plaque areas and volumes were smaller, and the percentages of necrotic core areas and volumes were larger in VH-TCFAs compared with non-TCFAs. Ruptured plaques in VH-IVUS analyses showed intermediate findings between VH-TCFAs and non-VH-TCFAs. In conclusion, culprit lesions in patients with ACS were more unstable and had greater amounts of necrotic core and smaller amounts of fibrofatty plaque compared with target lesions in patients with SAP.