BACKGROUND: Previous study showed that aortic knob calcification observed by chest X-ray was significantly correlated with the severity of coronary artery disease and was commonly observed in diabetic patients. OBJECTIVES: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between aortic knob calcification and the plaque composition in diabetic patients. METHODS: The presence of aortic knob calcification was assessed via posteroanterior view of chest X-ray. A total of 90 de novo coronary lesions in 30 consecutive diabetic patients were studied and plaque components were analyzed using VH-IVUS. VH-IVUS classified the color-coded tissue into four major components: fibrotic; fibro-fatty; dense calcium (DC); and necrotic core (NC). RESULTS: We detected aortic knob calcification in 7 patients (15 lesions). Patients with aortic knob calcification were older (70짹11 yrs vs. 62짹9 yrs, p=0.007), had higher N-terminal pro–B-type natriuretic peptide (937짹1378 pg/ml vs. 332짹536 pg/ml, p=0.005) and high-sensitivity C-reactive protein (hs-CRP) levels (1.26짹1.38 mg/dl vs. 0.53짹1.43 mg/dl, p=0.034). The %DC (15.8짹13.3% vs. 11.8짹11.5%, p=0.035) and %NC (25.3짹16.0% vs. 19.0짹11.8%, p=0.020) areas were significantly greater in lesions with aortic knob calcification at the minimum lumen sites, and the %DC (15.7짹9.5% vs. 11.6짹11.2%, p=0.032) and %NC (23.9짹12.7% vs. 17.2짹8.6%, p=0.017) volumes were significantly greater in lesions with aortic knob calcification. The reference segment %DC (9.0짹9.2% vs. 4.3짹5.3%, p=0.010) and %NC (18.9짹16.1% vs. 9.3짹7.7%, p=0.001) areas were significantly greater in lesions with aortic knob calcification. Multivariate analysis showed that %NC volume, hs-CRP, and age were the independent predictors of aortic knob calcification [Hazard ratio (HR); 1.170, 95% CI=1.053-1.299, p=0.003, HR=3.542; 95% CI=1.688-7.431, p=0.001, and HR=1.303; 95% CI=1.129-1.504, p<0.001, respectively]. CONCLUSIONS: VH-IVUS analysis demonstrates that diabetic patients with aortic knob calcification had higher inflammatory status and more vulnerable plaques (greater NC-containing plaques) compared with diabetic patients without aortic knob calcification.