BACKGROUND: Although myeloperoxidase (MPO) monitoring is predictive for cardiovascular outcomes in suspected acute coronary syndromes, the value of serial testing is unknown. METHODS: We investigated the relationship between serial MPO concentrations in 490 individuals with acute chest pain and incident major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPOwith the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott Architect assay. RESULTS: Plasma MPO concentrations during the first 16 h were higher in individuals who experienced MACE. Higher MPO quartiles predicted a greater likelihood of 6-month MACE at baseline [OR (95% CI), 2.4 (1.4-4.1), P = 0.001 for highest vs lowest quartile] and all subsequent time points, with strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7-20.9), P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among individuals whose cTnI remained within reference intervals (<0.028 μg/L). The lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and all other time points. Serial MPO monitoring predicted MACE risk better than baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002), including in individuals whose cTnI remained within reference intervals (c statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved accuracy for predicting 6-month MACE, reduced the number of missed MACE events from cTnI testing alone, and improved risk classification in 26.1% of patients. CONCLUSIONS: MPO concentrations are predictive of outcome up to 16 h after presentation with chest pain and predict events missed by cTnI testing, supporting a potential role in rapid patient triage.