Obesity is characterized by metabolic and vascular abnormalities. We examined the effects of weight loss on insulin sensitivity and arterial stiffness in overweight adults. Twelve (9 females; 3 males) overweight (body mass index, 30.3 +/- 3.7) adults (54.9 +/- 3.9 years) without diabetes or vascular disease were counseled by a registered dietician to lose weight over 6 months. Vascular structure, function, and wall mechanical properties were measured via ultrasound. Intravenous glucose tolerance test, 24-hour blood pressure, body composition (dual-energy x-ray absorptiometry), and lipids were also assessed. There were significant reductions in body mass (86.3 +/- 14.2 vs 79.5 +/- 13.8 kg, P < .0001) and percentage of fat (44.3% +/- 7.0% vs 41.0% +/- 8.5%, P < .01) after weight loss. There were significant improvements in total cholesterol (6.0 +/- 0.9 vs 5.0 +/- 0.8 mmol/L, P < .0001), low-density lipoprotein cholesterol (3.9 +/- 0.7 vs 3.2 +/- 0.6 mmol/L, P < .0001), triglycerides (3.4 +/- 2.3 vs 2.4 +/- 0.9 mmol/L, P < .05), and insulin sensitivity (3.3 +/- 1.7 vs 5.4 +/- 1.6 microU x 10(-4) min(-1) mL(-1), P < .0001) after weight loss. Brachial artery compliance (P < .05) and distensibility (P < .05) curves over the physiologic pressure range improved, whereas endothelial function and intima-media thickness remained unchanged. In overweight adults, 6 months of weight loss resulted in improvements in body composition, insulin sensitivity, lipid profile, and brachial artery compliance and distensibility.