Study objectives: Many patients with suspected acute coronary syndrome (ACS) are admitted from the emergency department (ED) because of the insensitivity of presentation ECGs and troponin levels. Ischemia-modified albumin (IMA) is a novel cardiac biomarker of acute cardiac ischemia. The US Food and Drug Administration has approved the use of a normal IMA concentration in low-risk (per history/physical examination, ECG, and troponin) patients with chest pain syndrome as an indication for safe ED discharge. Methods: We reviewed all studies identified by computerized literature and obtained proprietary data from the assay manufacturer that evaluated IMA as an ACS “rule-out” in the ED setting. For trials to be included, patients were required to present to the ED within 3 hours of symptom onset. For each study, the appropriate IMA diagnostic cutoff was defined by receiver operating characteristic curve analysis or a normal range study. Studies eligible for inclusion were required to document discharge diagnosis with respect to cardiac ischemia or pertinent clinical outcomes for a minimum of 30 days after the index presentation. Results: There were 8 studies meeting eligibility criteria. Three trials evaluated all nontraumatic chest pain presentations; 4 studies evaluated low- to moderate-risk patients with nondiagnostic ECG and a negative troponin at presentation; and 1 study evaluated patients initially triaged as high risk and requiring a cardiology consult. IMA in conjunction with troponin and ECG at presentation had a high negative predictive value for ACS at the index visit and during the follow-up period: 84% in a high-risk population and 91% to 100% in the low-risk population. Conclusion: IMA has a high negative predictive value for short-term adverse outcomes in a preselected low- to moderate-risk population of patients with suspected ACS and may be used to facilitate contraction of the risk stratification process for chest pain syndrome in the ED. Study objectives: Many patients with suspected acute coronary syndrome (ACS) are admitted from the emergency department (ED) because of the insensitivity of presentation ECGs and troponin levels. Ischemia-modified albumin (IMA) is a novel cardiac biomarker of acute cardiac ischemia. The US Food and Drug Administration has approved the use of a normal IMA concentration in low-risk (per history/physical examination, ECG, and troponin) patients with chest pain syndrome as an indication for safe ED discharge. Methods: We reviewed all studies identified by computerized literature and obtained proprietary data from the assay manufacturer that evaluated IMA as an ACS “rule-out” in the ED setting. For trials to be included, patients were required to present to the ED within 3 hours of symptom onset. For each study, the appropriate IMA diagnostic cutoff was defined by receiver operating characteristic curve analysis or a normal range study. Studies eligible for inclusion were required to document discharge diagnosis with respect to cardiac ischemia or pertinent clinical outcomes for a minimum of 30 days after the index presentation. Results: There were 8 studies meeting eligibility criteria. Three trials evaluated all nontraumatic chest pain presentations; 4 studies evaluated low- to moderate-risk patients with nondiagnostic ECG and a negative troponin at presentation; and 1 study evaluated patients initially triaged as high risk and requiring a cardiology consult. IMA in conjunction with troponin and ECG at presentation had a high negative predictive value for ACS at the index visit and during the follow-up period: 84% in a high-risk population and 91% to 100% in the low-risk population. Conclusion: IMA has a high negative predictive value for short-term adverse outcomes in a preselected low- to moderate-risk population of patients with suspected ACS and may be used to facilitate contraction of the risk stratification process for chest pain syndrome in the ED.