The ECG diagnosis of ischemic heart disease is made more difficult in the setting of left bundle branch block (LBBB). The ECG diagnosis of prior or remote myocardial infarction (MI) is extremely difficult in this setting. Furthermore, the associated--and expected--ST-segment--T-wave abnormalities of LBBB may mimic acute ischemic change. However, ECG detection of abnormalities arising from acute ischemic cardiac disease in the setting of LBBB can be valuable. Several strategies are available to the emergency physician (EP) to assist in the correct interpretation of this ECG pattern, including: a knowledge of the anticipated ST-segment--T-wave changes of LBBB and, consequently, the ability to recognize ischemic morphologies; the performance of serial ECGs demonstrating dynamic changes encountered in ischemic patients; and a comparison with previous ECGs. Three cases are reported in which an analysis of the 12-lead ECG in the setting of LBBB assisted the EP in establishing the correct diagnosis of acute MI and applying timely, appropriate therapy.