BACKGROUND AND AIMS: Current evidence underscores that oxidative stress (OS) is a pivotal factor in the formation of vulnerable plaques in individuals with coronary heart disease (CHD). The Oxidative Balance Score (OBS), a comprehensive measure of systemic OS, consists of 15 antioxidants and 5 pro-oxidants, with higher scores indicating greater antioxidant activity. We hypothesized that a high OBS would be associated with improved coronary plaque stability in CHD patients. METHODS AND RESULTS: A total of 635 patients diagnosed with CHD were included in this study. After accounting for confounding variables, we found a significant inverse association between higher OBS and the formation of thin-capped fibroatheroma (TCFA) (OR = 0.933, 95 % CI: 0.913, 0.953). This relationship exhibited a nonlinear pattern, plateauing at an OBS score of 18.1. Mediation analysis revealed that OBS significantly mediates the relationship between food intake (soy, grains, vegetables, fruits) and plaque stability (p <
0.05). CONCLUSION: Our findings indicate that a higher OBS is inversely associated with the presence of vulnerable plaques. Adopting a diet rich in antioxidants, characterized by increased consumption of soy, grains, vegetables, and fruits, along with an antioxidant-focused lifestyle, may serve as an effective preventive strategy to enhance plaque stability in CHD patients.