Background: The relationship between plasma biomarkers and vulnerable plaque is not well understood. Methods and Results: The 188 patients who underwent 3-vessel virtual histology (VH) intravascular ultrasound (IVUS) with peripheral blood sampling were enrolled. Plasma levels of matrix metalloproteinase 2 and 9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1, adiponectin, and macrophage migration inhibitory factor were measured. VH-IVUS-derived thin cap fibroatheroma (VH-TCFA) was defined as a necrotic core >10% of plaque area in the presence of >40% plaque burden. There were 38 patients with ruptured plaque and 150 patients without (107 patients with VH-TCFA, 43 patients without VH-TCFA) in culprit/target lesions. Among the biomarkers, only the MMP-9 level was significantly higher in patients with ruptured plaque (P=0.002). In the subgroup without ruptured plaque, significant differences in the levels of several biomarkers were not observed between patients with and without VH-TCFA. In both culprit/target and nonculprit/non-target vessels, the MMP-9 level showed a weak correlation with the total number of ruptured plaques (r=0.231, P=0.002). Conclusions: Among the biomarkers tested in this study, the MMP-9 level was significantly higher in patients with ruptured plaque. However, measurement of several biomarkers, including MMP-9, was incapable of predicting the presence of VH-TCFA. (Circ J 2010; 74: 332-336)