Purpose: Metabolic syndrome and endothelial dysfunction play a relevant role in the cardiovascular risk in post-menopause. The aim of the study was to assess the effects of a low-dose hemihydrate estradiol and drospirenone combination on cardiovascular risk parameters in postmenopausal women with metabolic syndrome. Materials and Methods: Twenty-eight healthy women (group A) and 28 women with metabolic syndrome (group B) were treated with hemihydrate estradiol one mg + drospirenone two mg. At recruitment and after six months, clinical and laboratory parameters of metabolic syndrome were evaluated. Endothelial function was assessed measuring the flow-mediated dilatation of the brachial artery and the intima-media thickness of the common carotid artery. Results: After six months an overall improvement of metabolism was observed in both groups reaching statistical significance for triglycerides, total cholesterolemia, and systolic pressure in group B. A trend to lower baseline flow-mediated dilatation was also found in group B. Conclusions: Drospirenone improves cardiovascular risk factors and does not impair endothelial function in menopausal women with metabolic syndrome.