BACKGROUND: Acute anterior myocardial infarction (MI) caused by proximal occlusion of the left anterior descending coronary artery (LAD), is associated with unfavourable outcome and should be recognized by simple noninvasive methods like the 12-lead electrocardiogram (ECG). METHODS: In a prospective post-hoc DANAMI-2 substudy we compared two pre-specified ECG patterns to determine the level of LAD occlusion. The ECG findings were correlated to coronary angiography from the acute phase. The impact on clinical outcome of ECG and angiographic signs of proximal versus distal LAD occlusion was studied. RESULTS: In 146 patients without confounding factors on the ECG, either ST-elevation>or=0.5 mm in lead aVL or any ST-elevation in lead aVR in association with precordial ST-segment elevation in at least two contiguous leads (including V2, V3 or V4) had a sensitivity of 94%, specificity of 49%, positive predictive value of 85% and negative predictive value of 71% to predict a proximal LAD lesion. Surprisingly, ECG or angiographic signs of lesion proximality were not associated with worse outcome at 30 day or 2.7 year follow-up. CONCLUSIONS: The site of occlusion in the LAD could be reliably predicted by 12-lead ECG in patients with acute anterior MI. The prognostic significance of the level of occlusion in the LAD in the modern era of acute ST-elevation MI treatment should be reassessed.