Although visceral obesity, a key abnormality in the metabolic syndrome, is an important risk for cardiovascular diseases, reduction in visceral fat is hard to achieve despite intensive efforts directed at lifestyle modification. The present study was designed to investigate whether ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1, reduces visceral fat in patients with metabolic syndrome. Seventy-eight outpatients (63·7 ± 10·4 years old) with metabolic syndrome were enroled and randomly assigned to receive either ezetimibe (10 mg/day) or nothing for 6 months. Changes in visceral fat were assessed by computed tomography. Treatment with ezetimibe significantly improved lipid profiles. Visceral fat was decreased 7·2%, from 161·3 ± 58·6 cm(2) to 148·4 ± 52·7 cm(2) (P < 0·05), and adiponectin was increased 7·7%, from 3·61 ± 3·10 μg/mL to 3·86 ± 3·62 μg/mL (P < 0·05), after ezetimibe therapy; these beneficial effects were not observed in the control group. The increase in the adiponectin level was correlated with the reduction in visceral fat after ezetimibe treatment. Furthermore, ezetimibe reduced fasting insulin levels (P < 0·05) and improved the homoeostasis model assessment of insulin resistance (HOMA-IR) (P < 0·05). Ezetimibe reduces visceral fat with beneficial effects on adiponectin and insulin resistance in patients with metabolic syndrome, suggesting a new therapeutic approach in such patients. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.