Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.