Although excess fat mass is linked to increased cardiovascular risk, the relation between vascular phenotype and degree of obesity in high weight categories is unknown. We examined brachial artery vasomotor responses using ultrasound in 203 consecutive patients with severe obesity (mean age 44 ± 11 years; body mass index [BMI] 46 ± 9 kg/m², range 30 to 72; and body weight 128 ± 29 kg, range 69 to 207). We studied a unique population in which 71% of subjects were characterized as morbidly obese (BMI ≥40 kg/m²), which included a 31% group of super-obese subjects (BMI ≥50 kg/m²). Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were examined as measures of endothelium-dependent and -independent dilation, respectively, in relation to clinical, hemodynamic, and metabolic variables. Endothelial function was significantly impaired in the highest compared with the lowest tertile of body weight (FMD 6.5 ± 4.6% vs 9.8 ± 4.8%, p <0.001), whereas nitroglycerin-mediated dilation was similar in all groups. Univariate correlates of FMD were gender, weight, waist circumference, BMI, diastolic blood pressure, and creatinine. In multivariate analysis, weight was a strong independent significant predictor of FMD (β = −0.23, p = 0.005) in addition to gender. Within an overweight population, cumulative weight burden remains strongly linked to progressive arterial dysfunction. In conclusion, these results suggest that cardiovascular risks intensify with higher degrees of obesity and underscore the importance of therapeutic weight loss interventions.