OBJECTIVE To determine the association between neighborhood socioeconomic status (NSES) and cardio-metabolic risk and whether this relationship differs by race/ethnicity. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis (n = 5750), ages 45-84 years, from 6 US counties, including 5 examinations from 2000 to 2012. We calculated a modified allostatic load (AL) index, indicating cardio-metabolic risk. NSES score included census-derived measures at census tract of residence. Mixed effects growth curve models were used to assess linear and non-linear associations between NSES and AL at baseline and over time. RESULTS Higher NSES was associated with lower AL across race/ethnic groups; considering NSES quintiles, significant associations were found only for the highest NSES quintiles (difference of -0.86 and -1.15 for white and Hispanic participants) vs. the lowest. We found no significant association between NSES and change in AL over time. CONCLUSIONS Our findings suggest that the relationship between NSES and AL reflects the health benefits of living in the most advantaged neighborhoods. CONCLUSIONS Understanding the impact of higher NSES on health effects may help identify interventions to effectively target high risk neighborhoods.