Background and aimsPlaque progression increases the risk of a cardiovascular event. This study aims to determine whether intraplaque neovascularization (NV) associates with a greater risk of plaque progression. MethodsBaseline and 12-month follow-up IVUS was used in combination with baseline OCT to assess 164 non-culprit plaques in 118 CAD patients. A generalized estimating equation approach with exchangeable correlation structure was used to correct for the dependency of repeated measurements. ResultsPatients were divided into two groups according to NV (52 patients with 62 NV plaques, 66 patients with 102 non-NV plaques). Non-culprit plaques in the NV group exhibited a more frequent occurrence of TCFA (p = 0.004), macrophage (p = 0.005), cholesterol crystal (p = 0.012), calcification (p = 0.030), thinner fibrous cap thickness (FCT) [(86.8 ± 55.1) vs. (127.4 ± 70.1) μm, p = 0.015], larger lipid arc [(219.5 ± 66.9) vs. (179.8 ± 61.4), p = 0.002] compared to the non-NV group. A large change in percent atheroma volume (PAV), plaque plus media cross-sectional area (P&M CSA), plaque volume, and plaque burden was observed from baseline to follow-up in the NV group. Changes in P&M CSA, plaque volume, and plaque burden showed significant differences in fibroatheroma with NV. Intraplaque NV could predict a high risk of plaque progression despite statin therapy [OR 6.521 (95% CI 2.457–17.308), p < 0.001]. ConclusionsNV might attenuate the benefits of statin therapy in plaque progression. This study may provide a new basis for anti-angiogenic strategies to prevent atherosclerotic plaque progression.