BACKGROUND: Coronary calcium is specific marker of atherosclerosis. Previous studies have shown that coronary calcium score was associated with plaque burden and morphology. However, little data are available about the relationship between coronary calcium score and plaque components. OBJECTIVES: We evaluated the relationship between coronary calcium score by cardiac computed tomography angiography (CCTA) and plaque components by virtual histology-intravascular ultrasound (VH-IVUS) in patients with coronary artery disease (CAD). METHODS: A 172 CAD patients with 250 coronary lesions who underwent CCTA were enrolled retrospectively and plaque components were analyzed using VH-IVUS. Coronary calcium score was assessed according to Agatston scoring method by CCTA: Group I [calcium Score = 0 (n=52)]; Group II [calcium Score = 1-100 (n=99)]; Group III [calcium Score = 101-400 (n=84)]; Group IV [calcium Score › 400 (n=15)]. VH-IVUS classified the color-coded tissue into four major components: fibrotic; fibro-fatty; dense calcium (DC); and necrotic core (NC). RESULTS: At the minimum lumen site, the percent DC area was greatest, in contrast the percent fibrotic area was smallest in Group IV (6.4짹7.7% vs. 11.1짹8.9% vs. 15.6짹10.9% vs. 18.4짹11.9%, p<0.001, and 62.7짹14.4% vs. 58.4짹13.7% vs. 49.8짹12.8% vs. 48.9짹13.2%, p<0.001, respectively). At the largest NC site, the percent DC area was greatest, and in contrast the percent fibrotic area was smallest in Group IV (8.4짹6.8% vs. 14.3짹8.9% vs. 17.1짹8.7% vs. 20.9짹9.9%, p<0.001, and 58.8짹12.2% vs. 50.8짹13.3% vs. 45.5짹11.4% vs. 43.3짹12.5%, p<0.001, respectively). The absolute DC and NC volumes were greatest, and percent DC volumes were greatest in Group IV (5.5짹6.6 mm3 vs. 11.0짹10.3 mm3 vs. 15.6짹13.6 mm3 vs. 36.6짹18.2 mm3, p<0.001, and 14.8짹18.2 mm3 vs. 19.5짹18.9 mm3 vs. 22.5짹19.1 mm3 vs. 41.7짹27.9 mm3, p<0.001, and 6.4짹5.3% vs. 11.0짹6.2% vs. 14.0짹6.5% vs. 20.0짹7.8%, p<0.001, respectively). The absolute plaque and DC and NC volumes and the percent DC volumes positively correlated with calcium score (r=0.470, p<0.001, r=0.318, p<0.001, r=0.313, p<0.001, respectively). But, the percent fibrotic volumes negatively correlated with calcium score (r=0.328, p<0.001). CONCLUSIONS: CAD patients with high calcium score had more vulnerable plaque components (greater DC and NC-containing plaques) compared with those with low calcium score.