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The benefit of emergency reperfusion therapy with fibrinolytics or primary percutaneous coronary intervention in patients with ST-segment elevation (STE) acute myocardial infarction (MI) is well known. However, what is not well known are which subgroups of MI patients with ST-segment depression (STD) on the 12-lead electrocardiogram (ECG) may benefit from emergent reperfusion therapy. Current clinical guidelines recommend against administering emergent reperfusion therapy to MI patients with STD on the ECG unless a true posterior MI is suspected. Overlooked subgroups of patients with STD on the initial ECG who may potentially benefit from emergent reperfusion therapy are patients with multilead STD with coexistent STE in lead aVR. This finding has been reported in MI patients with occlusion of the left main artery, occlusion of the proximal left anterior descending artery, and MI in the presence of severe multivessel coronary artery disease. Because these patients have a higher mortality in the setting of MI, we believe that this ECG finding be considered a STEMI equivalent and that patients with this finding receive consideration for emergent reperfusion therapy preferably at a center with both primary percutaneous coronary intervention and coronary artery bypass grafting capability. In this report, we present 3 such patients to heighten the awareness of the emergency physician to this phenomenon.