BACKGROUND: Previous studies have shown that coronary calcium score was associated with plaque burden and morphology. 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 74 CAD patients with 132 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=29)]; Group II [calcium Score = 1-100 (n=43)]; Group III [calcium Score = 101-400 (n=50)]; Group IV [calcium Score › 400 (n=10)]. 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 (6.0짹7.2% vs. 12.1짹9.8% vs. 13.8짹11.9% vs. 20.1짹14%, p=0.001, and 61.7짹15% vs. 57.4짹13% vs. 51.3짹13.5% vs. 49.5짹16.1%, p=0.006, respectively). At the largest NC site, the percent DC area was greatest, and in contrast the percent fibrotic area was smallest in Group IV (8.0짹7.4% vs. 14.7짹9.7% vs. 15.3짹9.3% vs. 23.8짹9.9%, p<0.001, and 57.8짹11% vs. 50.9짹11.9% vs. 47.6짹12.5% vs. 41.8짹14.4%, p=0.001, respectively). The absolute DC and NC volumes were greatest, and percent DC volumes were greatest in Group IV (4.9짹6 mm3 vs. 10.3짹9.1 mm3 vs. 12.9짹9.7 mm3 vs. 35.4짹21 mm3, p<0.001, and 12.5짹16.1 mm3 vs. 18.1짹20 mm3 vs. 19.4짹14 mm3 vs. 36.5짹27.8 mm3, p=0.005, and 6.5짹7% vs. 11.6짹6.5% vs. 12.4짹6.9% vs. 21.5짹7.5%, p<0.001, respectively). The absolute plaque and DC and NC volumes and the percent DC volumes positively correlated with calcium score (r=0.294, p=0.001, r=0.639, p<0.001, r=0.363, p<0.001, and r=0.436, p<0.001, respectively). 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.