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Previous angiographic studies have shown that almost two-thirds of vulnerable plaques are located in non-obstructive lesions. Possibly, the maximum necrotic core (Max NC) area is not always identical to the site of most severe stenosis. Therefore, the purpose of this study was to evaluate the potential difference in location between the maximum necrotic core area and the site of most severe narrowing as assessed by virtual histology intravascular ultrasound (VH IVUS). Overall, 77 patients (139 vessels) underwent VH IVUS. The Max NC site was defined as the cross section with the largest necrotic core area per vessel. The site of most severe narrowing was defined as the minimum lumen area (MLA). Per vessel, the distance from both the Max NC site and MLA site to the origo of the coronary artery was evaluated. In addition, the presence of a virtual histology-thin cap fibroatheroma (VH-TCFA) was assessed. The mean difference (mm) between the MLA site and Max NC site was 10.8 ± 20.6 mm (p < 0.001). Interestingly, the Max NC site was located at the MLA site in seven vessels (5%) and proximally to the MLA site in 92 vessels (66%). Importantly, a higher percentage of VH-TCFA was demonstrated at the Max NC site as compared to the MLA site (24 vs. 9%, p < 0.001). In conclusion, the present findings demonstrate that the Max NC area is rarely at the site of most severe narrowing. Most often, the Max NC area is located proximal to the site of most severe narrowing.