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Background: Acute coronary syndrome (ACS) resulting from culprit lesion in left main coronary artery (LMCA) can cause rapid hemodynamic deterioration. It is important to identify these patients early to facilitate timely revascularization. ST segment elevation in aVR greater than or equal to V 1 (aVR-V 1 ≥ 0) has been suggested as a sensitive predictor of LMCA disease. As a result of balanced forces, we hypothesized that ST deviation in V 6 greater than or equal to ST deviation in V 1 (V 6 -V 1 ≥ 0) might be a good determinant of LMCA disease. Methods: We compared admission 12-lead ECGs of ACS resulting from culprit LMCA lesion (n = 75, group I) with ACS resulting from culprit left anterior descending lesion (n = 81, group II). Group I was selected over a period of 10 years. We compared V 6 -V 1 ≥ 0 to aVR-V 1 ≥ 0 in both groups. We also looked at ratios of ST deviations in V 6 ,V 1 (V 6 /V 1 ≥ 1) and aVR,V 1 (aVR/V 1 ≥ 1) in patients where ST segment in V 1 was not isoelectric (group I = 54 and group II = 55). Results: ST deviation in V 6 was significantly greater in group I as compared to group II (P < 0.001). The reliabilities of V 6 -V 1 ≥ 0, V 6 /V 1 ≥ 1, aVR-V 1 ≥ 0, and aVR/V 1 ≥ 1 in predicting LMCA disease were determined. Conclusion: This is the largest series of ECG analysis on ACS resulting from culprit LMCA lesion. V 6 -V 1 ≥ 0 and V 6 /V 1 ≥ 1 were more sensitive in predicting LMCA as culprit vessel in comparison to previously reported greater ST segment elevation in aVR than V 1 .