Background: In takotsubo cardiomyopathy (TC), left ventricular dysfunction dramatically improves in a short time, and negative T waves (Neg T) with QT interval prolongation commonly appear, suggesting viable but sympathetically denervated myocardium. However, these findings are often observed in reperfused non-Q-wave anterior acute myocardial infarction (ant AMI). Methods: We compared 34 patients with TC and 237 with non-Q-wave ant AMI in whom occlusion followed by TIMI 3 flow of the left anterior descending coronary artery were documented by emergency coronary angiography. All patients were admitted within 6 h after symptom onset. After admission, ECGs with the greatest amplitude of Neg T (mean 2 days later) were analyzed. Results: As compared with patients with non-Q-wave ant AMI, those with TC were older (70±11 vs 61±11 years, p<0.01), more likely to be women (85% vs 21%, p<0.01), and had a lower peak creatine kinase level (289±298 vs 1505±921 mU/ml, p<0.01) despite a lower left ventricular ejection fraction on admission (41±10% vs 52±10%, p<0.01). TC was associated with a longer maximal QTc interval (642±93 vs 586±81 ms, p<0.01), a greater amplitude of maximal Neg T (10±4 vs 8±5 mm. p<0.05), and a greater number of leads with Neg T ≥1.0 mm (10±1 vs 6±2, p<0.01). Distribution of Neg T is shown in Figure, using the Cabrera sequence to display limb leads. In TC, Neg T was always observed in leads -aVR and V4-6, whereas Neg T was rare in lead V1. Neg T in lead -aVR (i.e., positive T wave in lead aVR) combined with no Neg T in lead V1 identified TC with 94% sensitivity, 95% specificity, and 94% accuracy, which was the highest diagnostic accuracy. Conclusions: As compared with non-Q-wave ant AMI, negative T waves appear more frequently and broadly in TC, suggesting that TC might be associated with more extensive viable but denervated myocardium. The combination of positive T wave in lead aVR and no negative Twave in lead V1 simply but accurately differentiates TC from non-Q-wave ant AMI.