It has been shown that a rise in creatine kinase MB bank (CK-MB) of > or = + 1.6 ng/mL in 2 hours is more sensitive and equally specific for detection of acute myocardial infarction (AMI) as compared with a 2-hour CK-MB > or = 6 ng/mL during the emergency department (ED) evaluation of chest pain. Because cardiac specific troponin I (cTnI) is thought to have similar early release kinetics as compared with CK-MB mass, we undertook a retrospective cohort study in 578 chest pain patients whose baseline CK-MB and cTnI was less than two times the hospital's upper limits of normal and who underwent a 2-hour CK-MB and cTnI to compare sensitivities and specificities of the 2-hour delta CK-MB (deltaCK-MB) and delta cTnI (delta cTnI) for AMI and 30-day Adverse Outcome (AO). Thirty day AO was defined as AMI, life-threatening complication, death, or percutaneous transluminal coronary angioplasty (PTCA)/coronary artery bypass graft (CABG) within 30 days of ED presentation. Optimum delta values were determined by choosing the smallest cutoff value greater than the assay precision where the deltaCK-MB and delta cTnI had a positive likelihood ratio for 30-day AO of > or = 15. A deltaCK-MB > or = +1.5 ng/mL was more sensitive than a deltaTnI > or = +0.2 ng/mL for AMI (87.7% versus 61.4%; P < .0005) and 30-day AO (56.7% versus 42.3%; P < .005). There were no differences in specificities for AMI and 30-day AO. Combining the two tests (MBdelta > or = +1.5 ng/mL and/or a deltaTnI > or = +0.2 ng/mL) resulted in an incremental increase in sensitivity of 89.5% for AMI and 61.9% for AO (P < .005). Patients with either a rise in CK-MB of > or = +1.5 ng/mL or rise in cTnI of > or = +0.2 ng/mL in 2 hours should receive consideration for aggressive antiischemic therapy and further diagnostic testing before making an exclusionary diagnosis of nonischemic chest pain.