Background: Because clinical and ECG findings of Tako-tsubo cardiomyopathy (TC) mimic those of anterior acute myocardial infarction (ant AMI), differential diagnosis is crucial for deciding whether reperfusion therapy is required. Methods: We compared admission ECGs between 33 patients (pts) with TC and 342 with a first ant AMI due to the left anterior descending coronary artery occlusion as documented by emergency coronary angiography. All pts were admitted within 6 h after symptom onset. ST-segment deviation was considered present if deviation was >0.5 mm in limb leads and >1.0 mm in precordial leads. Results: Pts with TC were older (70±11 vs 61±11 yrs, p<0.01), more likely to be women (75 vs 15%, p<0.01), and had a lower initial left ventricular ejection fraction (39±11 vs 46±11%, p=0.08) than those with ant AMI. On admission ECG, TC was more frequently associated with the absence of abnormal Q waves (42 vs 26%, p<0.05) and of inferior ST-segment depression (ST↓) (94 vs 51%, p<0.01), and lesser maximal ST-segment elevation (ST ↑) (5±5 vs 7±3 mm, p<0.01). Distribution of ST↑ is shown in Figure , using the Cabrera sequence for display of limb leads. In pts with TC, ST↑ most frequently occurred in lead -aVR, but was rare in lead V1. ST↑ in lead -aVR and no ST↑ in lead V1 was observed in 91% of pts with TC, as compared with only 4% of those with ant AMI (p<0.001). This finding identified TC with 91% sensitivity, 96% specificity, and 95% predictive accuracy, which were higher than those of other ECG variables. Conclusions: The presence of ST↑ in lead -aVR (i.e, ST↓ in lead aVR) and the absence of ST↑ in lead V1 strongly suggests TC. This ECG finding allows TC to be simply but accurately differentiated from ant AMI.