BACKGROUND AND OBJECTIVES: Rupture-prone plaque, characterized by a large necrotic core, thin fibrous cap and large number of inflammatory cells, is known to be associated with acute coronary syndrome (ACS) from several autopsy and animal studies. We sought to assess in-vivo lesion characteristics of culprit lesions in patients with ACS. SUBJECTS AND METHODS: One hundred consecutive patients (mean age 60.4 years, 70 males), who underwent percutaneous coronary intervention, were analyzed for intravascular ultrasound (IVUS) radiofrequency information using IVUS-virtual histology (VH) software. RESULTS: Patients with ACS (n=44, mean 59.7 years, 34 males) had a lower prevalence of hypertension (45.5% vs. 67.9%, p=0.024), higher level of high-sensitivity C-reactive protein (0.36+/-0.36 mg/dL vs. 0.22+/-0.27, p=0.043), longer lesion length (22.6+/-8.6 mm vs. 19.3+/-6.9 mm, p=0.036), and more plaque rupture (63.6% vs. 10.7%, p<0.001) than those without ACS (mean 61.0 years 36 males). The lesion analysis, at a minimal luminal area, revealed that patients with ACS had a larger plaque area (12.5+/-5.8 mm2 vs. 10.3+/-4.8 mm2, p=0.043) and necrotic core (1.7+/-1.4mm2 vs. 1.1+/-0.9 mm2, p=0.013) than those patients without ACS. Volumetric analysis over the lesion length showed that patients with ACS had larger plaque volume (9.9+/-4.0 mm3/mm vs. 8.3+/-3.4 mm3/mm, p=0.031) and necrotic core volume (1.3+/-1.0 mm3/mm vs. 0.8+/-0.6 mm3/mm, p=0.002) than those without ACS. The necrotic core volume was associated with the presence of ACS (beta=0.662, p=0.041) by the IVUS-VH findings. CONCLUSION: The results of this study suggest that the overall necrotic core volume, not the necrotic core area at the minimal luminal area, is associated with the clinical presentation of ACS.