Acute left main coronary artery (LMCA) occlusion may result in acute myocardial infarction (AMI) or sudden death. ST elevation in the aVR and V1 leads is reported to be valuable in recognizing LMCA occlusion. Early recognition of electrocardiogram (ECG) changes, such as reciprocal ST depression in other leads, is helpful in averting this disaster. This study aimed to determine the reciprocal ST segment depression of 12-lead ECGs associated with acute LMCA occlusion. From January 2000 to December 2004, 61 patients who underwent emergency percutaneous coronary intervention in 3 hospitals due to AMI associated with LMCA (n = 18) and a left anterior descending coronary artery (LADCA) (n = 43) proximal lesion were selected. Reciprocal ST segment depression occurred in leads aVF, V(2), V(3), V(4), V(5), and V(6) with significantly higher incidence in the LMCA group than in the LADCA group. Stepwise linear multivariate discriminant analysis indicated that ST segment depression in leads aVF, V(2), and V(4) could distinguish the LMCA group from the LADCA group. We concluded that reciprocal ST segment depression in leads V(2), V(4), and aVF of a 12-lead ECG is an important predictor of acute LMCA occlusion.