Background: Distal embolization during stent deployment carries a poor prognosis in patients with acute coronary syndrome (ACS). However, it is unclear which plaque components cause distal embolization and no-reflow after stent deployment in ACS patients. Objectives: We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between coronary plaque characteristics and no-reflow phenomenon in ACS patients. Methods: A total of 190 consecutive ACS patients were imaged using VH-IVUS. Angiographic no-reflow was defined as TIMI flow grade 0, 1, and 2 after stenting. VH-IVUS classified the color-coded tissue into four major components: fibrotic, fibro-fatty, dense calcium, and necrotic core (NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (��� 10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden ��� 40%. Results: Of 190 patients studied pre-stenting, no-reflow was observed in 24 patients (12.6%) at post-stenting. The absolute and % NC areas at the minimum lumen sites (1.6짹1.2 mm2 vs. 0.9짹0.8 mm2, p<0.001, and 24.5짹14.3% vs. 16.1짹10.6%, p=0.001, respectively), and the absolute and % NC volumes (30짹24 mm3 vs. 16짹17 mm3, p=0.001, and 22짹11% vs. 14짹8%, p<0.001, respectively) were significantly greater in no-reflow group compared with normal-reflow group. The presence of at least one TCFA and multiple TCFAs within culprit lesions were more common in no-reflow group compared with normal-reflow group (71% vs. 36%, p=0.001, and 38% vs. 15%, p=0.005, respectively). In the multivariate analysis, % NC volume was the only independent predictor of no-reflow (Odds ratio=1.126; 95% CI 1.045-1.214, p=0.002). Conclusion: VH-IVUS analysis demonstrates that post-stenting no-reflow occurs in lesions with a large NC area and more TCFAs in ACS patients. VH-IVUS is a useful tool of predicting the risk of no-reflow after stent deployment in ACS patients.