Background: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between high-sensitivity C-reactive protein (hs-CRP) levels and plaque components in 279 acute coronary syndrome (ACS) patients. Methods: We divided the patients into three groups according to the hs-CRP levels [lowest tertile < 0.07 mg/dl (n=93), middle tertile ���0.07, <0.4 mg/dl (n=93), and highest tertile ���0.4mg/dl (n=93)]. Thin-cap fibroatheroma (TCFA) was defined as focal, necrotic core (NC)-rich (��� 10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden ��� 40%. Results: Highest tertile group was most diabetics (20%, 27%, 40%, p=0.009) and had greatest plaque plus media volume (163짹139/mm3 vs. 201짹155/mm3 vs. 232짹176/mm3, p=0.013). Highest tertile group had greatest absolute and % NC volumes (13.6짹15.1 mm3 vs. 14.8짹14.2 mm3 vs. 23.7짹24.3 mm3, p<0.001, and 14.9짹8.7% vs. 16.0짹8.7% vs. 19.5짹10.2%, p=0.024, respectively). The culprit lesion TCFA was observed most frequently in highest tertile group (28% vs. 35% vs. 55%, p=0.006). By multivariable analysis, absolute NC volume was the independent predictor of hs-CRP elevation (OR; 1.03, 95% CI=1.06-1.21, p=0.004), and the hs-CRP was the independent predictor of TCFA (OR; 1.86, 95% CI=1.11-2.90, p=0.010). Conclusion: VH-IVUS analysis demonstrates that ACS patients with elevated hs-CRP have more vulnerable plaque component (NC-rich plaques and higher frequency of culprit lesion TCFA) compared with ACS patients with normal hs-CRP. KEY WORDS: Acute coronary syndrome; Plaque; Inflammation; Intravascular ultrasound