Background: Thin-cap fibroatheroma (TCFA) lesions are the most prevalent substrate of plaque rupture. Pathological studies showed diabetic patients had a greater amount of macrophage-infiltrated lipid-rich plaque compared with non-diabetic patients. This is consistent with a greater probability of TCFA and plaque rupture in diabetic patients. Objectives: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the plaque composition and the incidence of TCFA in diabetic acute coronary syndrome (ACS) patients. Methods: In 310 ACS patients (100 diabetics and 210 non-diabetics), de novo coronary lesions were studied and plaque components were analyzed. VH-IVUS classified the color-coded tissue into four major components: fibrotic; fibro-fatty; dense calcium (DC); and necrotic core (NC). We classified TCFA lesions as focal, NC-rich (��� 10% of the cross-sectional area) plaques being in contact with the lumen; and TCFA definition required a plaque burden ��� 40%. Results: The absolute and % NC areas at the minimum lumen sites (1.21짹0.88 mm2 vs. 0.86짹0.76 mm2, p<0.001, and 18.3짹11.6% vs. 15.3짹10.6%, p=0.029, respectively), and at the largest NC sites (1.85짹0.92 mm2 vs. 1.14짹0.83 mm2, p<0.001, and 30.1짹11.0% vs. 20.4짹9.6%, p<0.001, respectively), and the absolute and % NC volumes (16.9짹15.1 mm3 vs. 11.5짹11.4 mm3, p<0.001, and 17.3짹9.4% vs. 13.7짹7.5%, p<0.001, respectively) were significantly greater in diabetic patients compared with non-diabetic patients. The presence of at least one TCFA (60% vs. 42%, p=0.003) and multiple TCFAs (28% vs. 11%, p<0.001) within culprit lesions were more common in diabetic patients compared with non-diabetic patients. By multivariate analysis, diabetes mellitus was the only independent predictor of TCFA (HR: 2.139, 95% CI: 1.266-3.613, p=0.004). Conclusions: VH-IVUS analysis demonstrates that diabetic ACS patients had a greater NC-containing plaque and had a higher frequency of culprit lesion TCFAs compared with non-diabetic ACS patients.