Our objective was to determine whether moderate obesity (Body Mass Index [BMI] ≥ 30 kg/m²) is associated with impaired conduit and microvascular endothelial function, and whether men or women are more susceptible to impairment of endothelial function related to moderate obesity. Forty-one middle aged, nondiabetic moderately obese (BMI 34.7 4.0 kg/m 2 ) and nonobese (BMI 24.3 2.6 kg/m 2 ) subjects of both sexes underwent noninvasive studies of endothelial function (brachial reactivity) and measurements of endothelial-dependent vasodilation of gluteal subcutaneous arterioles to acetylcholine (Ach). Endothelium-dependent vasodilation to Ach was decreased in the moderately obese compared with the nonobese (P < 0.001). Stratified analysis based on sex showed impairment of arteriolar endothelial function in women BMI ≥ 30 kg/m 2 (P = 0.02), but not men. There was no difference between in vivo endothelial function flow-mediated dilation (FMD%) by BMI category. Sex-specific analysis showed FMD% was lower in women with BMI ≥ 30 kg/m 2 compared to those with BMI < 30 kg/m 2 (P = 0.02). No differences were seen in men based on BMI category (P = 0.18). In women, high sensitivity C-reactive protein (hsCRP) correlated with BMI (q = 0.68, P = 0.006). Moderate obesity is associated with impaired resistance arteriolar endothelial function. This is more prominent in women than men and is associated with systemic inflammation.