Brachial flow-mediated dilation (FMD) is a measure of endothelial nitric oxide bioavailability. Endothelial nitric oxide controls vascular tone and is likely to modify the ventricular muscle coupling mechanism. The association between left ventricular mass and FMD is not well understood. We assessed the association between left ventricular mass index (LVMI) and FMD in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a population-based study of 6814 adults free of clinical cardiovascular disease at baseline who were recruited from six US clinics. LVMI (left ventricular mass per body surface area) and FMD were measured in 2447 subjects. Linear regression analysis was used to evaluate the association. The subjects had a mean age of 61.2±9.9 years, 51.2% females with 34.3% Caucasians, 21.6% Chinese, 19.4% African Americans and 24.7% Hispanics. The mean body mass index (BMI) was 27.4±4.8 kg m⁻², 9.4% had diabetes, 11% were current smokers and 38% hypertensives. The mean±s.d. LVMI was 78.1±15.9 g m⁻² and mean±s.d. FMD was 4.4%±2.8%. In univariate analysis, LVMI was inversely correlated with FMD (r= -0.20, P<0.0001). In the multivariable analysis, LVMI was associated with FMD (β coefficient (se) = -0.50 (0.11), P<0.001 (0.5 g m⁻² reduction in LVMI per 1% increase in FMD)) after adjusting for age, gender, race/ethnicity, systolic blood pressure, diabetes mellitus, smoking, weight, statin use, antihypertensive medication use, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. The association between brachial flow mediated dilation and LVMI maybe independent of traditional CV risk factors in population based adults.