The purpose of this study was to determine the association between depression and coronary endothelial function and cardiac risk factors in men and women without obstructive coronary artery disease. Patients with no significant coronary artery disease who underwent invasive coronary endothelial function assessment with acetylcholine were studied. Men and women were divided into 2 groups: those with depression and those without. Endothelial function and risk factor profiles were compared between the 2 groups. Seven hundred fifty-nine patients were studied, 603 (79%) without depression and 156 (21%) with depression. Patients with depression were more likely to be women (71% vs 60%, p = 0.02), have greater body mass indexes (29.9 +/- 6.7 vs 28.2 +/- 5.9 kg/m(2), p = 0.002), and be diabetic (12% vs 6%, p = 0.02). Depressed patients also had higher levels of C-reactive protein (0.35 vs 0.30 mg/dl, p = 0.02). There was no difference in the change in coronary blood flow or diameter in response to acetylcholine between the 2 groups in men and women. In conclusion, the results of this study demonstrate that depression is not associated with coronary endothelial dysfunction in men and women without significant coronary artery disease. It is, however, associated with a cluster of cardiac risk factors that are linked to the progression of atherosclerotic disease.