With the exception of contrast-enhanced cardiovascular magnetic resonance imaging, clear distinction of takotsubo cardiomyopathy from anterior wall myocardial infarction cannot be achieved currently by simple and noninvasive tests. The aim of this study was to examine the role of inferior ECG leads in distinguishing these two conditions. From January 2004 to June 2006, eight female patients suffering from takotsubo cardiomyopathy were identified by the Mayo Clinic criteria. The clinical and ECG features were compared with 27 consecutive sex- and age-matched patients with anterior wall myocardial infarction admitted to the Coronary Care Unit within the same period. The observed ECG features were then verified with that of 62 published cases of takotsubo cardiomyopathy. Takotsubo cardiomyopathy patients had similar left ventricular ejection fraction (35.0% +/- 5.7% vs 38.2% +/- 6.4%, P = 0.829), lower peak creatinine kinase level (461 +/- 330 U/l vs 2723 +/- 1826 U/l, P = 0.020), more ST-segment elevation in the inferior leads (50% vs 7.4%, P = 0.016), and virtually no ST-segment depression in inferior leads (0% vs 48.2%, P = 0.015) compared with patients who had anterior wall myocardial infarction. ST-segment elevation of >or=1.0 mm in lead II had 62.5% sensitivity and 92.6% specificity in detecting takotsubo cardiomyopathy. The observed ECG characteristics were comparable with those in the literature. In patients who present with anterior wall myocardial infarction, the absence of ST-segment depression or ST-segment elevation in inferior leads, especially if the ST-segment in lead II >or= III, is highly suggestive of takotsubo cardiomyopathy.