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We compared the sensitivity of three commonly used cardiac markers between two subpopulations, those who came to the Emergency Department (ED) late (6-24 h) after their symptoms began, and those who arrived earlier (<6 h), in a prospective comparative trial. Among all adult patients who presented to our ED with symptoms suggestive of acute myocardial infarction (MI), we drew serum for myoglobin, CK-MB, and troponin I upon arrival (time 0) and 2 h later. Outcomes, including acute MI, were determined. Sensitivities for all three markers between the subpopulations who arrived fewer than 6 h from symptom onset were compared to those who arrived later (6-24 h). We enrolled 346 eligible subjects, 36% of whom described cardiac symptoms as beginning 6 or more hours earlier; 14% suffered acute MIs. For time 0, the sensitivity of all three markers for acute MI was significantly higher among those subjects with symptoms of 6 or more hours' duration as compared to those with less. For troponin I, the increase in sensitivity between these two subpopulations approached 300%. At the time of the 2-h sample, the differences in sensitivities were much less and were not statistically significant. We conclude that cardiac marker values obtained at time 0 among Emergency Department patients who arrive 6 or more hours after cardiac symptom onset provide significantly higher sensitivities as compared to those obtained in patients who arrive earlier. For troponin I, the increase in sensitivity approaches threefold.