Purpose: The aim of the study is to evaluate the clinical usefulness of a TWI in the lead aVL of 12-lead ECG for predicting the left ascending artery (LAD) lesion, high risk, and 30-days mortality in patients with acute coronary syndrome (ACS). Methods: A total of 275 patients who underwent coronary angiography under the diagnosis of ACS were analyzed retrospectively from Jan 2012 to December 2013. Results: A total of 355 patients underwent coronary angiography. Of these, 275 patients (77.5%) were diagnosed with ACS. Of these, 187 patients (68.0%) had a left LAD lesion. Of these, 111 patients (59.3%) had a mid-LAD lesion. Of these, only 23 patients (22.5%) showed a TWI in the aVL lead. However, regarding the prediction of the high risk group, if there is a TWI in the aVL, when compared with patients without a TWI in the aVL, the high risk rate is four times higher in the univariable logistic regression analysis and 2.687 times higher in the multivariable logistic regression analysis. Conclusion: A TWI in the lead aVL of ECG of patients with chest pain in the ER was closely associated with high risk of ACS patients.