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Introduction: Ideal cardiovascular health (CVH) promotion is effective for cardiovascular disease prevention. Whether increased CVH score improves oxidative stress is less clear. Our study examined the correlation between changes in ideal CVH status and oxidative stress.Hypothesis: Improvement in CVH score is correlated with changes in oxidative stress.Methods: A total of 569 actively working adult employees (51±11 years, 64% women, 21% Black) underwent a health partner-mediated lifestyle intervention. Serial counseling was delivered by a trained HP focused on promoting clinical self-knowledge and adoption of a healthier lifestyle, based on the subject’s personal schedule. Anthropometric, dietary and laboratory measurements were obtained at baseline and 1- and 2-year follow-up visits. Plasma levels of reduced (glutathione) and oxidized (cystine) aminothiols were measured by high performance liquid chromatography at baseline and follow-up to assess oxidative stress. Ratios of oxidized to reduced aminothiols (cystine/glutathione) were calculated. Linear mixed-effects model was used to examine the correlation between the changes in CVH score and changes in oxidative stress metrics overall 2 years follow-up.Results: Over 2-years, cystine (p=0.01) improved while cystine/glutathione (p=0.03) and glutathione (p<0.001) decreased in the entire cohort. At baseline, CVH score was significantly associated with improvement in cystine by -0.39 μM (95% CI, -0.45, -0.32), glutathione by 0.22 μM (95% CI, 0.14, 0.29) and cystine/glutathione by -0.40 (95% CI, -0.46, -0.33). Overall, one unit increase in the CVH score was associated with a decrease of -0.33 μM (95% CI, -0.42, -0.24) in cystine and -0.38 (95% CI, -0.46, -0.29) in the cystine/glutathione ratio over 2 years. Similarly, an improvement in CVH score by one unit at 2 years was associated with improvement in glutathione by 0.30 μM (95% CI, 0.21, 0.39). Furthermore, reduction in BMI, systolic blood pressure and fasting glucose level was significantly associated with improvement in cystine (all p<0.01), glutathione (all p<0.01) and cystine/glutathione (all p<0.01) over 2 years.Conclusion: Improvement in CVH with a lifestyle intervention was associated with early and sustained improvement in oxidative stress. Whether the impact of changes in CVH metrics on oxidative stress improves long-term morbidity and mortality needs further investigation in a controlled design.