Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients. Objective: The objective of this study was to evaluate the effects of 6 months of metformin administration on endothelial structure and function in women with PCOS. Design: This was a prospective, baseline-controlled, clinical study. Setting: The study was performed at University Federico II (Naples, Italy). Patients: Thirty young normal-weight women with PCOS without additional metabolic or cardiovascular diseases were studied. Interventions: Metformin (850 mg daily) was administered for 6 months. Mean Outcome Measures: The main outcome measures were complete hormonal profile, including total testosterone, SHBG, dehydroepiandrosterone sulfate, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75-g 2-h oral glucose tolerance test; plasma endothelin-1 concentrations (picomoles per liter ± SD); serum lipid profile; brachial artery baseline diameter (millimeters ± SD), diameter after reactive hyperemia (millimeters ± SD), and flow-mediated dilation (percentage ± SD); and the intima media thickness (millimeters ± SD) on both common carotid arteries. Results: After treatment, SHBG levels and the free androgen index changed significantly (P < 0.001). High-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins and plasma endothelin-1 levels were significantly (P ± 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant difference was observed in brachial artery baseline diameter (3.24 ± 0.30 vs. 3.0 ± 0.30), flow-mediated dilation (14.30±1.90 vs. 15.70±1.50) (P<0.01, each), diameter after reactive hyperemia (3.70±0.30 vs. 3.55±0.10) (P<0.05), and intima media thickness (0.53 ± 0.09 vs. 0.40 ± 0.07) (P < 0.001) after metformin treatment in comparison with baseline values. Conclusions: A 6-month course of metformin improves endothelial structure and function in young, normal-weight women with PCOS. Copyright © 2005 by The Endocrine Society.