BACKGROUND: Previous study showed that aortic knob calcification observed by chest X-ray or fluoroscopy was correlated with the severity of coronary artery disease in diabetic patients. OBJECTIVES: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between aortic knob calcification and the plaque components in diabetic patients. METHODS: The presence of aortic knob calcification was assessed via posteroanterior view of chest X-ray or fluoroscopy at the time of coronary angiogram. A total of 137 de novo coronary culprit lesions in 137 consecutive diabetic patients were studied and plaque components were analyzed using VH-IVUS according to the presence (n=45)/absence (n=92) of aortic knob calcification. VH-IVUS classified the color-coded tissue into four major components: fibrotic; fibro-fatty; dense calcium (DC); and necrotic core (NC). RESULTS: Patients with aortic knob calcification were significantly older (68짹8 yrs vs. 62짹9 yrs, p<0.001) and had significantly higher high-sensitivity C-reactive protein levels (1.97짹1.33 mg/dl vs. 0.48짹1.35 mg/dl, p=0.005) compared with patients without aortic knob calcification. IVUS plaque burden at the minimum lumen sites (68짹11% vs. 61짹13%, p=0.002), and the absolute and %NC volumes (30짹26 mm3 vs. 20짹19 mm3, p=0.003, and 23.4짹10.3% vs. 17.4짹8.9%, p=0.005, respectively) and the absolute and %DC volumes (17짹12 mm3 vs. 11짹12 mm3, p=0.010, and 13.3짹7.3% vs. 9.6짹7.9%, p=0.011, respectively) were significantly greater in lesions with aortic knob calcification compared with those without aortic knob calcification. Multivariable analysis showed that age [Odds ratio (OR); 1.233, 95% CI=1.121-1.355, p<0.001], high-sensitivity C-reactive protein (OR; 1.871, 95% CI=1.090-2.943, p=0.007), absolute DC volume (OR; 1.020, 95% CI=1.050-1.178, p=0.003), and absolute NC volume (OR; 1.026, 95% CI=1.057-1.199, p<0.001) were the independent predictors of aortic knob calcification. CONCLUSIONS: VH-IVUS analysis demonstrates that diabetic patients with aortic knob calcification were older, had greater NC and DC-containing plaques, and higher inflammatory status compared with diabetic patients without aortic knob calcification.