Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular dysfunction (LVD). However, studies have not elucidated the mechanisms of action and overall effects of EECP in patients with LVD. The purpose of this study was to investigate the effects of EECP on endothelial function in peripheral conduit arteries and exercise capacity (peak VO2) in patients with LVD. Patients with ischemic LVD (EF 34.5±4.2%; n=9), and patients with symptomatic CAD and preserved LV function (EF 53.5±6.6%; n=15), were studied before and after 35 1‐hr sessions of EECP. Brachial (bFMD) and femoral (fFMD) artery flow‐mediated dilation were evaluated using high‐resolution ultrasound. EECP elicited similar significant improvements in the following FMD parameters amongst the CAD and LVD groups, respectively: absolute bFMD (+53% and +70%); relative bFMD (+50% and +74%); bFMD normalized for shear rate (+70% and +61%); absolute fFMD (+33% and +21%); and relative fFMD (+32% and +17%) (P≥0.05 between groups). EECP significantly improved plasma levels of nitrate/nitrite (NOx) (+55% and +28%; μmol/L) and prostacyclin (6‐keto‐PGF1α) (+50% and +70%); and improved peak VO2 (+36% and +21%), similarly in both the CAD and LVD groups, respectively; (P≥0.05 between groups). Despite reduced LV function, EECP therapy significantly improves peripheral vascular function and functional capacity similar in magnitude to that observed in CAD patients with preserved LV function. This article is protected by copyright. All rights reserved.