Obesity is associated with impaired endothelial-dependent flow-mediated dilation, a precursor to hypertension and atherosclerosis. Although dieting generally improves cardiovascular risk factors, the direct effect of different dietary strategies on vascular endothelial function is not known. The purpose of this study was to test the hypothesis that a low-fat (LF) diet improves endothelial function compared with an isocaloric low-carbohydrate (LC) diet. Obese (n=20; body mass index: 29 to 39; mean systolic blood pressure: 107 to 125 mm Hg) and otherwise healthy volunteers were randomly assigned to either the American Heart Association modeled LF (30% fat calories) diet or an isocaloric LC Atkins' style diet (20 g of carbohydrates) for 6 weeks (4-week weight loss and 2-week maintenance phase). Brachial flow-mediated dilation and dilation to nitroglycerin were measured with ultrasound using automated edge detection technology (baseline, week 2, and week 6). Blood pressure, weight loss, and cholesterol profiles were measured throughout the study. Weight loss was similar in LF (100+/-4 to 96.1+/-4 kg; P<0.001) and LC (95.4+/-4 to 89.7+/-4 kg; P<0.001) diets. Blood pressure decreased similarly in both groups (LF: 8/5 mm Hg; LC: 12/6 mm Hg) at 6 weeks. After 6 weeks, the percentage of flow-mediated dilation improved (1.9+/-0.8; P<0.05) in the LF diet but was reduced in the LC diet (-1.4+/-0.6; P<0.05) versus baseline. Dilation to nitroglycerin and lipid panels was similar at 0, 2, and 6 weeks. Despite similar degrees of weight loss and changes blood pressure, LF diets improved brachial artery flow-mediated dilation over LC diets. LF diets may confer greater cardiovascular protection than LC diets.