Volatile organic compounds (VOCs) are ubiquitous environmental toxicants with pre-clinical evidence of decreased vascular health. Research to date has focused on single VOC metabolites and data is lacking on the effects on human vascular health. Many VOCs are strongly correlated with similar exposure sources. Though the compounding effects are poorly defined, they are likely to increase the overall toxicity. Therefore, we examined single VOC metabolites and mixtures’ association with flow mediated dilation (FMD), an index of vascular health. We recruited adult participants into a CV risk cohort, aged 25-70 years, from 2018 and 2019. A panel of urinary VOC metabolites were measured in 308 non-smoking participants who had completed brachial artery FMD. Regression analysis of 16 VOC analytes was tested for associations with %FMD and models were adjusted for covariates selected a priori including age, sex, diabetes and ACE inhibitors. We examined the joint effect of MU, 3HPMA, CEMA, CYMA, DHBMA, 2HPMA, 2MHA, and AAMA mixtures on log-transformed %FMD using quantile-based g-computation models adjusted for the covariates above and for correlated VOC metabolites that were not associated with FMD in single metabolite analyses. The mean %FMD was 7.1 % ± 4.7%. VOC metabolites that were predictors of decreased %FMD in fully adjusted models were 3HPMA (β=-1.275; 95% CI= -2.402, -0.148; p=0.027), CEMA (β= -1.204; 95% CI= -2.051; -0.357 p=0.006), AAMA (β=-1.125; 95% CI= -2.156, -0.094; p=0.033), 2HPMA (β= -1.035; 95% CI= -1.847, -0.222 p=0.013), and 2MHA (β=-0.623; 95% CI= -1.123, -0.124; p=0.015). Most VOC metabolites had fair to moderate correlations in bivariate analyses (Spearman correlation from 0.06 to 0.60). We found that a quartile increase in the VOC mixture was associated with 20% lower percent FMD (ψ -0.18; 95%CI= -0.35, -0.02; p=0.027) in adjusted models. We found the overall mixture effect was driven primarily by 3HPMA, followed by CYMA, CEMA, 2MHA, and AAMA. Therefore, the main driver of the association between the VOC mixture and decreased vascular function is acrolein and to a lesser extent acrylonitrile. Future research could focus on identifying sources of exposure to these VOCs to promote better vascular health among non-smokers.