Background: Previous trials using intravascular ultrasound(IVUS) have demonstrated that the lipid lowering therapy with statin decrease plaque volume and increase plaque echogenecity in patients with coronary artery disease. We examined whether statins clinically alter the composition of coronary atherosclerotic plaques of humans by in vivo IVUS-Virtual Histology(VH) analysis. Methods: This was a prospective, single-center study to assess the effect of 6 months of treatment with statin to induce the change of plaque composition in non-percutaneous coronary intervention(PCI) sites of the culprit vessel with <50% diameter stenosis among 26 patients with acute coronary syndrome(ACS). One target segment was determined in a non-PCI site (>5 mm proximal or distal to the PCI site) with a reproducible index side branch or from the ostium of target vessel. Results:In 6 months after statin therapy, no significant change was demonstrated in mean percentage of the lipid core(16.3 짹 7.4% to 13.4 짹 7.7%, p=0.10), whereas plaque volume and LDL-cholesterol level were significantly reduced. Of 26 patients, four different types of atherosclerotic plaque were identified: fibrotic(n=5), fibrocalcific(n=9), fibroatheroma with thick cap(n=3), or fibroatheroma without thick cap(TCFA, n=9). There was a significant reduction of lipid core percentage only in the type of TCFA (19.8 짹 4.0 % to 9.9 짹 5.2 %, p=0.003). Conclusions:IVUS-VH may be useful to evaluate effects of statin on plaque composition in vivo. Specifically, percentage of lipid core was significantly reduced in the type of TCFA which suggest that the change of plaque composition following statin therapy might be different according to plaque stability in patients with ACS.