BACKGROUND AND METHODS: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family highly expressed in adipocytes and macrophages. Recent studies indicate a key role for circulating FABP4 in the pathogenesis of atherosclerosis and type 2 diabetes. We described an additional role for FABP4 in the development of cardiac dysfunction in obesity. Therefore, FABP4 seems to be a target in the prevention and treatment of metabolic and cardiovascular disorders in obesity with high potential for future therapeutic applications. However, a safe pharmacological therapy is not yet available. Lipoprotein apheresis is an established therapy for severe and otherwise untreatable hypercholesterolemia which increases life expectancy in patients at high-risk for cardiovascular events. We therefore investigated the acute effect of lipoprotein apheresis on FABP4 serum levels in 64 high-risk patients (25 women, 39 men) under regular apheresis treatment. RESULTS: FABP4 levels were significantly reduced by 23.2 ± 1.8% by apheresis treatment. Although women had higher FABP4 levels than men (53.5 ± 8.3 ng/ml vs. 30.7 ± 4.3 ng/ml), reduction rate after lipoprotein apheresis was similar in both genders. Among the apheresis methods investigated, immunoadsorption of lipoproteins was most effective in lowering circulating FABP4. CONCLUSION: These data suggest that the reduction of FABP4 serum levels may contribute to the preventive effect of lipoprotein apheresis on cardiovascular events.