Objective-To evaluate the use of cardiac troponin I (cTnI), creatine kinase-MBmass (CK-MBmass), myosin light chain 1 (MLC 1), and myoglobin in identifying "high risk" patients with chest pain who will experience serious cardiac events (SCEs) in hospital. Design-Prospective study. Setting-University affiliated medical centre in Philadelphia, USA. Patients-208 patients with chest pain, at > 7% risk of acute myocardial infarction (MI), but without new ST segment elevation on their presenting EGG. Interventions-cTnI, CK-MBmass, MLC 1, and myoglobin concentrations were obtained on admission (0 hour) and at 4, 8, 16, and 24 hours. Main outcome measures-The sensitivity, specificity, positive and negative predictive value, and pre- and post-test probabilities of patients suffering an SCE in hospital were determined. SCEs included cardiac death, acute MI, cardiac arrest, Life threatening cardiac arrhythmia, cardiogenic shock, and urgent coronary revascularisation. Results-Admission concentrations of all markers were poor predictors of SCEs in hospital but improved substantially at subsequent timepoints. cTnI and CK-MBmass were consistently the most useful prognostic indicators. If both were negative at 0, 4, and 8 hours, then 99% (95% confidence interval 96% to 100%) of patients remained free from SCEs. The only SCEs not thus predicted were revascularisation procedures and associated complications. Additional tests after 8 hours, or the inclusion of additional markers, did not improve predictive accuracy further. Conclusions-Patients with high risk clinical features on admission who have negative cTnI and CK-MBmass concentrations at 0, 4, and 8 hours later have a favourable in-hospital prognosis and could be considered for early triage out of coronary care units.