Background: The association between infarct artery location, reperfusion success, and clinical outcomes after primary percutaneous coronary intervention(PCI) has not been characterized. We examined the infarct artery-specific impact of epicardial and myocardial flow and reperfusion after primary PCI for acute myocardial infarction. Methods: Among 2082 patients undergoing primary PCI in the CADILLAC trial, myocardial blush grade, TIMI flow grade, ST-segment resolution, and clinical outcomes were analyzed according to the infarct artery. Results: Baseline clinical characteristics did not significantly differ between patients experiencing infarction in the left anterior descending(LAD, 37%) versus left circumflex(18%) and right coronary artery(46%) distributions. Baseline left ventricular function was reduced, and collateral flow was less commonly present in patients with infarction involving the LAD. Achievement of final TIMI-3 flow, grade 3 myocardial blush, and ST-segment resolution >70%was also significantly less common in anterior infarction. Patients with anterior versus nonanterior infarction had significantly higher mortality at 30 days(3.4%vs 1.3%, P=.0006) and 1 year(6.5%vs 2.9%, P< .0001) and had increased 1-year rates of reinfarction(3.6%vs 1.7%, P=.009) and ischemic target vessel revascularization(16.1%vs 11.7%, P=.006). By multivariate analysis, LAD infarction was a powerful independent predictor of 1-year mortality(odds ratio 2.45, P=.009). Conclusions: Acute myocardial infarction involving the LAD distribution is associated with reduced left ventricular function, less frequent collateral flow, impaired myocardial perfusion and decreased reperfusion success, findings associated with reduced survival, and increased major adverse cardiac events compared with other vascular territories. These data provide mechanistic insights to the adverse prognosis of patients with anterior infarction. Background: The association between infarct artery location, reperfusion success, and clinical outcomes after primary percutaneous coronary intervention (PCI) has not characterized. We examined the infarct artery-specific impact of epicardial and myocardial flow and reperfusion after primary PCI for acute myocardial infarction . Methods: Among 2082 patients undergoing primary PCI in the CADILLAC trial, myocardial blush grade, TIMI flow grade, ST-segment resolution, and clinical outcomes were analyzed according to the infarct artery. Results: Baseline clinical characteristics did not vary differ between patients experiencing infarction in the left anterior descending (LAD, 37%) versus left circumflex (18%) and right coronary artery (46%) distributions. Baseline left ventricular function was reduced, and collateral flow was less commonly present in patients with infarction involving the LAD Achievement of final TIMI-3 flow, grade 3 myocardial blush, and ST-segment resolution> 7 0% was also significantly less common in anterior infarction. Patients with anterior versus nonanterior infarction had significantly higher mortality at 30 days (3.4% vs 1.3%, P = .0006) and 1 year (6.5% vs 2.9%, P <.0001 ) and had increased 1-year rates of reinfarction (3.6% vs 1.7%, P = .009) and ischemic target vessel revascularization (16.1% vs 11.7%, P = .006). By multivariate analysis, LAD infarction was a powerful independent predictor of 1-year mortality (odds ratio 2.45, P = .009). Conclusions: Acute myocardial infarction involving the LAD distribution is associated with reduced left ventricular function, less frequent collateral flow, impaired myocardial perfusion and decreased reperfusion success, findings associated with reduced survival, and increased major adverse cardiac events compared with other vascular territories. These data provide mechanistic insights to the adverse prognosis of patients with anterior infarction.