For patients admitted to the emergency department (ED) with suspected acute coronary syndrome, we compared results of a rapid, point-of-care whole blood assay for cardiac troponin I (Abbott i-STAT, Abbott Point-of-Care, East Windsor, NJ) (Tn-P) with an automated central laboratory plasma assay (Siemens TnI-Ultra, Siemens Medical Solutions Diagnostics, Tarrytown, NY) (Tn-U). Clinical data were obtained during a 6-month period during which ED patients were screened by Tn-P, with retesting of elevated results by Tn-U. Of 5,909 Tn-P results, 573 (9.7%) were elevated; these and a random selection of 137 negative specimens were retested by Tn-U. Of the specimens with elevated results, 4.5% retested negative by Tn-U, even though Tn-U typically gave about 50% higher results and had a lower manufacturer-specified 99th percentile cutoff. Of the negatives, 5.8% retested as elevated by Tn-U, but with levels no higher than 0.1 ng/mL (0.1 microg/L). Rapid whole blood testing for cardiac troponin I gave generally reliable patient classifications compared with plasma testing in the central laboratory, but besides missing small elevations, produced some apparent false-positives.