Background: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between anemia and plaque components in 1,141 lesions in 740 patients with acute coronary syndrome (ACS). Methods: Anemia was defined according to criteria of the World Health Organization, (i.e., hemoglobin levels <13 g/dl in men and <12 g/dl in women) and we compared VH-IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia group (569 patients, 881 lesions). Thin-cap fibroatheroma (TCFA) was defined as a necrotic core (NC) ��� 10% of plaque area in at least 3 consecutive frames without overlying fibrous tissue in the presence of ��� 40% least 3 plaque burden. Results: At the minimum lumen site, anemia group had greater %NC area compared with non-anemia group (20짹11% vs. 18짹12%, p=0.033). Anemia group had greater %NC and dense calcium (DC) volumes (21짹9% vs. 19짹9%, p=0.001, and 12짹7 vs. 10짹7%, p=0.002, respectively) compared with non-anemia group. Hemoglobin level correlated negatively with absolute NC volume (r=-0.235, p<0.001), %NC volume (r=-0.209, p<0.001), absolute DC volume (r=-0.211, p<0.001), %DC volume (r=-0.193, p<0.001), and correlated positively with absolute fibrotic (FT) volume (r=0.205, p=0.001), %FT volume (r=0.164, p=0.001), absolute fibro-fatty (FF) volume (r=0.187, p=0.001), and %FF volume (r=0.134, p<0.001). Independent predictors of TCFA by multivariate analysis were diabetes mellitus [odds ratio (OR): 2.213, 95% CI: 1.403-3.612, p=0.006), high-sensitivity C-reactive protein (OR: 1.143; 95% CI 1.058-1.304, p=0.012), microalbuminuria (albumin levels of 30 to 300 mg/g of creatinine) (OR: 2.124; 95% CI 1.041-3.214, p=0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, p=0.028). Conclusions: VH-IVUS analysis demonstrates that anemia at the time of clinical presentation was associated with vulnerable plaque component in patients with ACS.