Background: The diagnostic work-up of patients with acute chest pain in the emergency department (ED) is a challenging task. Serial troponin testing is required to rule-out acute myocardial infarction.Objective: To evaluate the value of myeloperoxidase (MPO) testing in sensitive cardiac troponin I (cTnI) negative patients with suspected acute coronary syndromes (ACS) in the routine setting of an ED.Methods: MPO was assessed in 432 consecutive patients presenting to the ED with ACS. In 266 patients, serial blood samples were available. After 6 weeks, major adverse cardiac events (MACE) were assessed. MPO and cTnI were measured in all available samples. For cTnI, a sensitive assay was used. Cut-off values were derived from an independent sample of 300 healthy volunteers.Results: Incidence of MACE in our population was 13%. MPO levels revealed sensitivity (Sens) of 82.1% and specificity (Spec) of 37.2% for MACE compared with 60.7% Sens and 61.4% Spec for sensitive cTnI. In serial sensitive cTnI negative patients (n=218), MACE incidence was 6.4%. MPO continued to demonstrate significant discriminatory power for the prognosis of MACE. Multivariate analyses confirmed these findings.Conclusion: MPO has an independent prognostic value overall and most notably in patients tested negative with a higher sensitive cardiac troponin I assay. MPO could be a promising biomarker for the initial evaluation of patients in chest pain units and is worth further investigation.