Abstract BACKGROUND: Endothelial dysfunction contributes to the manifestation of stable and unstable coronary syndromes in patients with established coronary artery disease (CAD). Enhanced external counterpulsation (EECP) is a noninvasive therapeutic modality for patients with CAD, non responsive to medical and/or surgical treatment. The aim of this research was to determine the long-term effect of EECP on endothelial function via releasing angiogenic factors, NO (nitric oxide) and VEGF (vascular endothelial growth factor), in patients with CAD. METHODS: The study was performed on 19 consecutive patients with ischemic coronary artery disease. All subjects were treated with EECP 1-h per day, 5 days a week, over 7 weeks (totally 35 h). Serum level of VEGF and nitrite (stable NO metabolite) concentration was measured before EECP, after 24th day, at the end of course (35th day), and at 1 and 3 months after completion of EECP treatment. RESULTS: After 35 hours of EECP, there was a trend toward increase (31.5 ± 14.7%) in nitrite level compared with baseline (11.12±3.17vs 9.65±1.36mg/L) but it wasn’t significant. Results of 1and 3 month follow-up after treatment showed that, the nitrite levels significantly increased compared with the baseline. During the course of EECP therapy, plasma VEGF levels increased progressively .Significant increase in plasma levels of VEGF were began from second sampling session of our study (24th day) and reached to maximum 3 month after EECP therapy. CONCLUSION: In this prospective study that assessed the effects of EECP on plasma nitrite and VEGF levels, it has been demonstrated that EECP progressively increases nitrite and VEGF levels during the course of therapy. These significant changes continued 3 months after EECP therapy.