Proximal occlusion of the left anterior descending coronary artery (LAD) results in a less favorable prognosis in coronary angiography. Therefore, it is important to determine whether there are significant lesions in LAD by electrocardiography (ECG) before coronary angiography. Twelve-lead ECG was compared in 130 patients with significant lesions (≥70% stenosis) confined to proximal part of the LAD (P LAD group) and 492 patients with normal coronary angiography (control group). Fifty-nine patients in the P LAD group and 18 patients in the control group had signs of anterior myocardial infarction as shown by ST elevation (≥1.0 mV) in two consecutive pericardial leads or the presence of a pathological Q wave. An inverted U wave (biphasic T wave) in leads V1 to V4 had a sensitivity of 49.3% (35/71) in P LAD patients without signs of anterior myocardial infarction (MI) and 96.6 % (57/59; specificity, 66.6%; positive predictive value, 90.9 %) in the P LAD patients with signs of anterior MI. In the P LAD patients with signs of anterior MI, T inversion in V4–V5 had a lower sensitivity (67.0% [40/59]) than an inverted U wave. ST depression in inferior leads and ST depression in V5 were not useful markers of proximal LAD occlusion. In conclusions, an inverted U wave in V1 to V4 (or in each of these leads) and T inversion in V4–V5 are the best predictors of significant proximal LAD lesion, especially in patients with ECG findings of anterior MI.