The frequency and distribution of thin-cap fibroatheromas (TCFA) have important clinical implications. We evaluated the frequency and distribution of TCFA identified by virtual histology intravascular ultrasound (VH-IVUS) in acute coronary syndrome (ACS) and stable angina pectoris (SAP). Preintervention 3-vessel VH-IVUS was performed in 105 patients with ACS and 107 with SAP. The length of left anterior descending artery imaged was 72 +/- 16 mm-54 +/- 12 mm in the left circumflex and 92 +/- 19 mm in the right coronary. VH-IVUS-derived TCFA (VH-TCFA) had a necrotic core > or =10% of plaque area without overlying fibrous tissue in a plaque burden > or =40%. There were 76 ruptured plaques (55 in ACS and 21 in SAP) and 439 VH-TCFA (262 in ACS and 177 in SAP, 2.5 +/- 1.5 vs 1.7 +/- 1.1 TCFA per patient with ACS and with SAP, respectively; p <0.001). Twelve patients with ACS and 1 with SAP had multiple ruptured plaques (p <0.001); 76 patients with ACS and 58 with SAP had multiple VH-TCFA (p = 0.009). Presentation of ACS was the only independent predictor for multiple ruptured plaques (p = 0.013) or multiple VH-TCFA (p = 0.011). Eighty-three percent of VH-TCFA were located within 40 mm of the coronary: 111 < or =10 (25%), 110 from 11 to 20 (25%), 83 from 21 to 30 (19%), and 61 from 31 to 40 mm (14%). The axial distribution of VH-TCFA was similar in patients with ACS and those with SAP and was similar to the axial distribution of ruptured plaques. In conclusion, 3-vessel VH-IVUS imaging showed a higher frequency of VH-TCFA in primary and secondary lesions in patients with ACS compared with those with SAP, but showed a similar clustering of VH-TCFA in the proximal 40 mm of each coronary artery.