Early EKG changes may contribute to predict the site of coronary artery occlusion during acute inferior myocardial infarction (MI). Its interpretation is relevant to therapeutic clinical decisions. We have prospectively evaluated early EKG changes of 40 consecutive patients with acute inferior MI and correlated them with the site and location of the coronary artery culprit lesion. Proximal right coronary artery occlusion was characterized by negative ST-T wave changes in leads D1 and aVL and ST segment elevation in leads D3 > D2. However the most distinctive EKG pattern of proximal right coronary artery occlusion was ST segment elevation with positive T wave in V4R (specificity 96%, predictive value 89%, p < 0.001). Distal right coronary artery occlusion was characterized by a positive T wave without ST segment elevation in V4R. Finally circumflex coronary artery occlusion was defined by a positive R/S > 1 relationship in V1, ST segment elevation in V5 and V6. Again lead V4R with flat or negative ST-T wave morphology had the highest predictive value for circumflex coronary artery occlusion (100%). Thus early EKG changes may contribute to precise the site and location of coronary artery occlusion and may help to implement clinical therapeutic strategies in patient with inferior MI. Right precordial leads are most useful in the EKG interpretation of inferior MI.