BACKGROUND: Myeloperoxidase (MPO) concentrations predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but the prognostic role of MPO in stable patients with known atherosclerotic burden is unclear. METHODS: We examined plasma MPO concentrations and their relationship with prevalent significant coronary artery disease (defined as >50% stenosis in any coronary vessel) and incident major adverse cardiovascular events (MACEs), including death, myocardial infarction, and stroke, in a 3-year prospective follow-up study of 1895 patients undergoing elective coronary angiography. RESULTS: The median plasma MPO concentration was 101 pmol/L (interquartile range 68-187 pmol/L). Patients with plasma MPO concentrations 7gt; 322 pmol/L (14.6% of population) had increased risk of developing future MACEs [hazard ratio (HR) 1.78, 95% CI 1.33- 2.37, P<0.001], and MPO as a single variable predictor of MACE showed an area under the ROC curve of 0.67. After adjusting for traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein (hsCRP), increased MPO concentrations remained significantly associated with incident MACEs over the ensuing 3-year period (HR 1.71; 95% CI 1.27-2.30, P<0.001). In patients with increased hsCRP, MPO≤322 pmol/L was associated with lower event rates than observed with MPO > 322 pmol/L. CONCLUSIONS: PlasmaMPO concentrations provide independent prognostic value for the prediction of longterm incident MACEs in a stable, medically managed patient population with coronary artery disease. In individuals with increased hsCRP concentrations, we observed lower risk of incident MACEs when concomitant MPO concentrations were low vs when MPO concentrations were high.