Backgrounds: Vulnerable plaque is known as underlying lesion of acute coronary syndrome (ACS), which is mainly evaluated in autopsy studies. We sought to evaluate in vivo tissue characterization of plaque responsible for ACS. Methods: Study subjects consisted of 151 consecutive patients with ACS (mean 61.7 yrs old, 112 males) and 181 consecutive patients with stable angina (SA, mean 61.5 yrs old, 121 males), who underwent virtual histology-intravascular ultrasound (VH-IVUS) examination. Each volumetric data was adjusted for the different lesion length by dividing by lesion length. Results: ACS patients had higher incidence of smoker (48.3% vs. 26.3%, p<0.001) than SA patients. The percent composition of plaque did not show any significant difference between two groups in terms of both over the entire lesion length and at the minimal lumen site. ACS patients had higher fibrous (3.81짹2.06mm³/mm vs. 3.18짹1.99mm^3/mm, p=0.005) and necrotic core volume (1.22짹0.91mm³ vs. 0.97짹0.72mm³/mm, p=0.005) than SA patients. At the minimal lumen site, fibrous (5.30짹3.09mm² vs. 4.26짹2.68mm², p=0.001) and necrotic core area (1.65짹1.23mm² vs. 1.32짹1.08mm², p=0.010) were also higher in ACS patients than SA patients. Gray scale IVUS data showed that ACS patients had higher remodeling index (1.01짹0.19 vs. 0.95짹0.18, p=0.003), longer lesion length (19.78짹8.14mm vs. 17.89짹7.56mm, p=0.030), higher plaque burden over the entire lesion length (59.17짹7.51% vs. 56.49짹8.78%, p=0.039), and higher plaque burden at the minimal luminal area site (73.82짹8.07% vs. 70.01짹9.99%, p<0.001) than SA patients. Multivariate analysis including variables showing significant differences in univariate analysis revealed that necrotic core volume (beta=0.226, p=0.004) and remodeling index (beta=0.174, p=0.025) were the independent factors for ACS. Conclusions: This study suggests that underlying lesion for ACS is associated with increased necrotic core volume as well as positive vascular remodeling.