The metabolic syndrome (MetS) often accompanies obesity and contributes to the increased risk of atherothrombotic events with increased body fatness. Indeed, the risks for coronary artery disease and acute vascular events are greater with obesity combined with MetS compared with obesity alone. Endothelial release of tissue-type plasminogen activator (t-PA) is a key defense mechanism against thrombosis and has been shown to be impaired with obesity. The aim of the present study was to determine whether the presence of MetS exacerbates endothelial fibrinolytic dysfunction in obese adults. Net endothelial release of t-PA was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside in 47 sedentary adults: 15 normal weight (age 57 ± 2 yr; body mass index 22.9 ± 0.5 kg/m2), 14 obese but otherwise healthy (55 ± 1 yr; 29.4 ± 0.3 kg/m2), and 18 obese with MetS (55 ± 2 yr; 32.3 ± 1 kg/m2). MetS was established according to National Cholesterol Education Program ATP III criteria. Net release of t-PA antigen to bradykinin was ∼50% lower ( P < 0.01) in the obese (from 2.5 ± 1.9 to 37.1 ± 5.3 ng·100 ml tissue−1·min−1) and obese with MetS (from 0.4 ± 0.8 to 32.5 ± 3.8 ng·100 ml tissue−1·min−1) compared with normal-weight (from 0.9 ± 1.0 to 74.3 ± 8.1 ng·100 ml tissue−1·min−1) subjects. However, there were no significant differences in the capacity of the endothelium to release t-PA in the obese and obese with MetS adults. These results indicate that the presence of the MetS does not worsen the obesity-related endothelial fibrinolytic dysfunction.