Multiple unstable plaques have been demonstrated by various imaging techniques in culprit and nonculprit arteries in patients with acute coronary syndromes, but the frequency with which clinical manifestations of multiple unstable plaques occur is unclear. To estimate this frequency in patients who present within 6 hours with ST-elevation myocardial infarction, we studied electrocardiograms and cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2 trial of 17,073 patients; this trial compared intravenous bivalirudin with unfractionated heparin before administration of streptokinase. Twenty-six patients (3.6%) developed recurrent ST elevation in a different territory. Of all the patients who developed ST elevation in a different territory, 50% (13 of 26) did so during the 48 hours of randomized antithrombin therapy compared with 29% (140 of 487) of those who developed recurrent ST elevation in the index territory (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552 patients (71%) with confirmed reinfarction, and ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO-2 enrollees, respectively). These data suggest that clinical manifestation of multiple unstable plaques of recurrent ST elevation and reinfarction in a territory different from that of the index ST elevation myocardial infarction after intravenous fibrinolytic and antithrombin therapies is rare.