Endothelial dysfunction (ED), a key event in the initiation/progression of atherosclerosis, is common in patients with coronary artery disease (CAD) despite control of conventional risk factors. Recently, novel non-lipid risk factors for CAD have emerged, among which C-reactive protein (CRP) has been suggested to be linked to ED. However, the relationship between CRP and ED in CAD patients treated with statins who have optimal plasma cholesterol and blood pressure control is unclear. The aim of this study was to explore the role of CRP as a predictor of ED in patients optimally treated with statins. We recruited consecutive patients with CAD undergoing elective CABG surgery, excluding patients with inflammatory diseases that may lead to elevated CRP. Endothelial function was assessed ex vivo in saphenous vein (SV) rings obtained at time of CABG. Of 115 patients, 99 (mean age 66 ± 0.9; 90% male) were optimally treated with statins, with cholesterol levels <5.0 mmol/L (mean 3.1 ± 0.7) and triglycerides 1.2 ± 0.1 mmol/l. All values are mean ± SEM. These patients had BMI 26.9 ± 0.4 kg/m2, waist circumference 99.8 ± 1.0 cm, systolic blood pressure 138.7 ± 2.2 mmHg, diastolic blood pressure (DBP) 74.3 ± 1.1 mmHg, fasting glucose 6.2 ± 0.2 mmol/L, and CRP 2.4 ± 0.2 mg/L. Vascular reactivity of preconstricted SV rings was assessed in 77 of these patients. Maximal relaxation to the endothelium-dependent vasodilator acetylcholine (Ach; 10-9-10-4 mol/L) was 25.5 ± 2.3 % and to the endothelium-independent vasodilator sodium nitroprusside (SNP; 10-9-10-4 mol/L) was 125.8 ± 7.0 %. In univariate analysis, CRP (r=-0.3), waist circumference (r=-0.19) and BMI (r=-0.2) were significantly inversely correlated with relaxation to Ach (all P<0.05). In stepwise multivariate analysis, the only independent predictor of relaxation to Ach was CRP (r=-0.3; P=0.025). Relaxation to SNP was not associated with any of the variables. In multivariate analysis to assess correlates of plasma CRP in this group of patients, the only independent predictors were BMI (r=0.34), DBP (r=0.25) and fasting glucose (r=0.3) – all P<0.01. In statin-treated CAD patients with low cholesterol levels undergoing CABG, CRP is the only independent predictor of ED. These data support a link between CRP and ED even in patients treated with currently recommended doses of statins.