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Abstract: Introduction: Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls. Materials and Methods: Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (±5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean±SEM. Results: Twenty cases (mean age 42±4.0 years, 11 females) and 39 controls (mean age 41±2.9, 22 females) were studied. FMD was 5.7±0.8% in cases (95% CI: 4.1 to 7.3) and 6.8±0.5% (5.7 to 7.9) in controls (p=NS). Plasma von Willebrand factor was 128±11.3% and 134.2±16.1% in cases and controls, respectively (p=NS). Soluble P-selectin and soluble CD40L were 94.1±4.9 ng/ml and 0.7±0.1 ng/ml in cases and 87.7±4.0 ng/ml and 1.0±0.2 in controls, respectively (p=NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups. Conclusions: Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system. [Copyright &y& Elsevier]