OBJECTIVE To investigate the effects of tumor necrosis factor (TNF)- alpha antagonism with etanercept (ENC) on endothelial functions in patients with active rheumatoid arthritis (RA). METHODS A total of 21 patients with RA were enrolled in this prospective study. Eleven of them (8 women, 3 men mean age 47.0+/-10.1 years) with high disease activity despite the conventional treatment were assigned to Group 1 and were given ENC treatment twice a week (25 mg SC injection) for 12 weeks. Ten patients with RA (8 women, 2 men mean age 55.0+/-6.4 years) under conventional methotrexate and prednisone therapy were assigned as Control group (Group 2). Endothelium-dependent and -independent vasodilator responses of the brachial artery were assessed by high-resolution ultrasound. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured at baseline and at the post treatment period. Mann-Whitney U and Wilcoxon tests were used to compare the data and correlation analysis was performed using Pearson correlation test. RESULTS Endothelium-dependent vasodilatation improved from 5.2+/-0.8% to 7.9+/-1.3% (p=0.04) in ENC group, while no significant change was observed in the control group (from 6.6+/-1.1% to 7.0+/-1.8% p=0.67). No significant changes were found in endothelium-independent vasodilatation and baseline brachial artery diameters in both groups. A significant reduction in ESR and CRP were observed in patients receiving ENC (from 16.2+/-6.8 to 9.2+/-5.1 mm/h, p=0.003 and from 14.68+/-3.4 to 9.25+/-3.7 mg/L, p=0.003, respectively). CONCLUSION Treatment with ENC for 12 weeks significantly improved endothelial function in patients with active RA compared to those under conventional therapy. The findings of the present study support the hypothesis that the use of TNF-alpha blockers in patients with active RA may reduce the high incidence of cardiovascular complications.