Baseline plasma myeloperoxidase (MPO) levels have been shown to independently predict the early risk of myocardial infarction (MI) in patients presenting with chest pain. In addition, baseline MPO levels have been demonstrated to predict the development of adverse cardiac events up to 6 months after an acute coronary syndrome (ACS). However, in contrast to other biomarkers, there are no data about the long-term independent predictive value of baseline MPO values in patients with ACS. The present study investigated the long-term prognostic significance of baseline MPO levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Administration Medical Center. All patients were followed prospectively for the development of death and MI, and follow-up data were available for all patients at 24 months. After controlling for different baseline clinical, laboratory, and angiographic variables, baseline plasma MPO values were a strong and independent predictor of MI at 24 months by multivariate analysis. Using the median MPO value of the entire cohort of patients (i.e., 20.34 ng/ml) as a prespecified cutoff, the MI-free survival at 24 months for the group whose baseline MPO values were < or =20.34 ng/ml was 88% compared with 74% in those whose values were >20.34 ng/ml (p = 0.0249 by log-rank test). In conclusion, these data demonstrate that baseline MPO levels independently predict MI at 2 years in patients with ACS.