Patients with subclinical hypothyroidism (SCH) have impaired endothelial function probably related to dyslipidemia. The present study compares the effects of simvastatin versus levothyroxine (LT-4) treatment on lipid profile and endothelial function in patients with SCH. Fifty-nine patients with newly diagnosed SCH were enrolled. Patients were randomized into 3 groups to receive no treatment (n = 19), LT-4 (n = 20), or simvastatin (n = 20). We measured endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) at baseline and after 8 months. Serum total cholesterol, triglycerides and LDL-cholesterol were significantly lower following simvastatin. EDV increased significantly in simvastatin treatment group (7.5% +/- 3.3% vs 14.0% +/- 4.5% (P < 0.01). The improvement of EDV correlated with the percent decrease of LDL-cholesterol (rho = 0.68, P < 0.01). Although LT-4 therapy caused a trend towards an increase in EDV compared to baseline, statistical significance was not achieved. EIV remained unchanged in all three groups. Simvastatin but not LT-4 treatment significantly improves EDV of the brachial artery and dyslipidemia in patients with SCH. Improvement in brachial artery endothelial function may be related in part to a hypolipidemic effect of simvastatin treatment.