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Studies have revealed that vasa vasorum(VV) neovascularization is vital for the progression and vulnerability of coronary atherosclerotic plaques. The correlation between VV, plaque constituents, and the no-reflow phenomenon (NRP) in percutaneous coronary intervention (PCI) remains elusive. We explored plaque constituents in iMap-intravascular ultrasound (iMap-IVUS) and NRP during PCI for VV lesions. We studied 166 coronary lesions in 166 patients with acute coronary syndromes (ACS) (118 lesions with VV) undergoing pre-intervention intravascular ultrasound (IVUS). We evaluated the diversity in plaque morphological status and post-PCI results based on the presence or absence of VV. The lesions with VV group had significantly higher high-sensitivity C-reactive protein (hs-CRP) levels than the lesions without VV group (8.41 ± 4.98 vs 4.19 ± 3.69 mg/L, P <.001). The frequency of after-stent deployment thrombolysis in myocardial infarction (TIMI) flow grades 0, 1, and 2 was remarkably greater in lesions with VV than in those without VV (22.9% vs 10.4%, P< .001). Plaques at the minimum lumen, necrotic core (1.26 ± 0.64 vs 0.92 ± 0.61 mm2, P< .001; 20.95 ± 7.19 vs 13.34% ± 6.54%, P< .001), and fibrous areas (4.23 ± 1.32 vs 3.92 ± 1.01 mm2, P= .006; 61.01 ± 9.41 vs 56.92% ± 11.42%, P =.001) were considerably larger in the lesions with VV than in those without VV. In addition, densely calcified plaques (0.41 ± 0.26 vs 0.81 ± 0.59 mm2, P< .001; 3.63 ± 2.19 vs 7.18% ± 2.01%, P< .001) were considerably smaller in the lesions with VV than in those without VV. Multivariate analyses revealed that VV and plaque volume were independent predictors of NRP after stent deployment (odds ratio [OR]: 5.13, 95% confidence interval [CI]: 1.19–15.32, P= .002; OR: 4.79, 95% CI: 1.08–9.01, P= .005). Lesions with VV exhibited considerable plaque vulnerability in patients with ACS, and they displayed more NRP during PCI. VV and plaque volume were independent predictors of NRP after stent deployment.