Cushing's syndrome (CS) as represented by chronic glucocorticoid excess is associated with increased rate of cardiovascular morbidity and mortality. Because endothelial dysfunction is an early event of atherosclerosis, we investigated whether endothelial dysfunction is associated with CS and reversible. Twenty-one CS patients due to different causes were studied for vascular endothelial function by ultrasound measurement of flow-mediated vasodilation (FMD), among whom 12 patients were re-evaluated after surgical and medical treatment; 12 age- and gender-matched subjects served as control. Percent (%) FMD in CS patients (5.8+/-1.9 %) was significantly (p =0.0014) lower than that in control subjects (8.1+/-1.7 %). In CS patients, %FMD showed significant (p < 0.01) negative correlations with morning serum cortisol levels (r =-0.58) and 24-h urinary free cortisol excretion (r =-0.58). After surgical and medical treatment in CS patients, morning cortisol levels significantly (p =0.0025) decreased from 23.4 [15.6-37.3] to 10.2 [7.7-12.9] microg/dL, whereas %FMD significantly (p =0.0024) increased from 5.2+/-1.9 to 7.8+/-2.3 %; changes of %FMD after treatment significantly (p =0.0004) and inversely correlated with those of morning cortisol levels (r =-0.85), but not with those of body mass index, blood pressure, glycemic or lipid profiles. Taken together, the present study clearly revealed that endothelial dysfunction in CS patients is related to hypercortisolemia and reversible after treatment, suggesting the possible role of cortisol excess in the development of endothelial dysfunction, thereby possibly leading to increased cardiovascular complications.