ImportanceCardiovascular disease is the leading cause of death in the US. However, little is known about the association between cumulative environmental burden and cardiovascular health across US neighborhoods.ObjectiveTo evaluate the association of neighborhood-level environmental burden with prevalence of cardiovascular risk factors and diseases, overall and by levels of social vulnerability.Design, Settings, and ParticipantsThis was a national cross-sectional study of 71 659 US Census tracts. Environmental burden (EBI) and social vulnerability indices from the US Centers for Disease Control and Prevention (CDC) and Agency for Toxic Substances and Disease Registry were linked to the 2020 CDC PLACES data set. Data were analyzed from March to October 2023.ExposuresThe EBI, a measure of cumulative environmental burden encompassing 5 domains (air pollution, hazardous or toxic sites, built environment, transportation infrastructure, and water pollution).Main Outcomes and MeasuresNeighborhood-level prevalence of cardiovascular risk factors (hypertension, diabetes, and obesity) and cardiovascular diseases (coronary heart disease and stroke).ResultsAcross the US, neighborhoods with the highest environmental burden (top EBI quartile) were more likely than those with the lowest environmental burden (bottom EBI quartile) to be urban (16 626 [92.7%] vs 13 414 [75.4%]), in the Midwest (5191 [28.9%] vs 2782 [15.6%]), have greater median (IQR) social vulnerability scores (0.64 [0.36-0.85] vs 0.42 [0.20-0.65]), and have higher proportions of adults in racial or ethnic minority groups (median [IQR], 34% [12-73] vs 12% [5-30]). After adjustment, neighborhoods with the highest environmental burden had significantly higher rates of cardiovascular risk factors than those with the lowest burden, including hypertension (mean [SD], 32.83% [7.99] vs 32.14% [6.99]; adjusted difference, 0.84%; 95% CI, 0.71-0.98), diabetes (mean [SD], 12.19% [4.33] vs 10.68% [3.27]; adjusted difference, 0.62%; 95% CI, 0.53-0.70), and obesity (mean [SD], 33.57% [7.62] vs 30.86% [6.15]; adjusted difference, 0.77%; 95% CI, 0.60-0.94). Similarly, neighborhoods with the highest environmental burden had significantly higher rates of coronary heart disease (mean [SD], 6.66% [2.15] vs 6.82% [2.41]; adjusted difference, 0.28%; 95% CI, 0.22-0.33) and stroke (mean [SD], 3.65% [1.47] vs 3.31% [1.12]; adjusted difference, 0.19%; 95% CI, 0.15-0.22). Results were consistent after matching highest and lowest environmentally burdened neighborhoods geospatially and based on other covariates. The associations between environmental burden quartiles and cardiovascular risk factors and diseases were most pronounced among socially vulnerable neighborhoods.Conclusions and RelevanceIn this cross-sectional study of US neighborhoods, cumulative environmental burden was associated with higher rates of cardiovascular risk factors and diseases, although absolute differences were small. The strongest associations were observed in socially vulnerable neighborhoods. Whether initiatives that address poor environmental conditions will improve cardiovascular health requires additional prospective investigations.