Human albumin has the ability to bind cobalt at the N-terminus. The exposure of circulating albumin to ischemic tissue alters the ability of albumin to bind cobalt, probably through a mechanism involving free-radical production. The Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal binding, and elevation of the ACB test is thought to be an early indicator of myocardial ischemia. In a previous multicenter study of chest pain patients presenting to the emergency department (ED), this test demonstrated high negative predictive value and sensitivity in the sample collected at presentation for predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h later. Since the completion of that report, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) have redefined the criteria for the diagnosis of acute myocardial infarction (AMI). The data from the multicenter ACB study were re-examined using the new diagnostic criteria for AMI to determine if combining the ACB test with troponin improved the sensitivity of either assay used alone for early diagnosis of AMI. Assay values were compared to either the final discharge diagnosis made at each site or to a diagnosis of AMI using the strict application of the ESC/ACC guidelines. Using the criterion of physician's discharge diagnosis and using blood collected at ED presentation, the cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p < 0.001 over cTnI alone) when both tests were used in combination. The sensitivity of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7% and at the >6- to 12-h time-point was 93.5%, but they were not significantly improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria, the combination also resulted in a statistically significant higher diagnostic sensitivity on blood collected at presentation. These data indicate a possible role of the ACB test in the early triage of patients with chest pain.