OBJECTIVES We sought to determine if beta-blocker therapy improves clinical outcomes of acute myocardial infarction (AMI) after successful primary percutaneous coronary intervention (PCI). BACKGROUND We have shown that pre-treatment with beta-blockers has a beneficial effect on short-term clinical outcomes in patients undergoing primary PCI for AMI. It is unknown if beta-blocker therapy after successful primary PCI improves prognosis of AMI. METHODS We analyzed clinical, angiographic, and outcomes data in 2,442 patients who underwent successful primary PCI in the Primary Angioplasty in Acute Myocardial Infarction-2 (PAMI-2), PAMI No Surgery-on-Site (PAMI noSOS), Stent PAMI, and Air PAMI trials. We classified patients into beta group (those who received beta-blockers after successful PCI, n = 1,661) and no-beta group (n = 781). We compared death and major adverse cardiac events (MACE) (death, reinfarction, and ischemia-driven target vessel revascularization) at six months between groups receiving and not receiving beta-blockers. RESULTS At six months, beta patients were less likely to die (2.2% vs. 6.6%, p < 0.0001) or experience MACE (14 vs. 17%, p = 0.036). In multivariate analysis, beta-blockers were independently associated with lower six-month mortality (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.26 to 0.73, p = 0.0016). Beta-blocker therapy was an independent predictor of lower six-month events in high-risk subgroups: ejection fraction less than or equal to50% (death: OR 0.34, 95% Cl 0.19 to 0.60, p = 0.0002) or multi-vessel coronary artery disease (CAD) (death: OR 0.26, 95% CI 0.14 to 0.48, p < 0.0001; MACE: OR 0.57, 95% CI 0.41 to 0.80, p = 0.0011). CONCLUSIONS Treatment with beta-blockers after successful primary PCI is associated with reduced six-month mortality, with the greatest benefit in patients with a low ejection fraction or multi-vessel CAD. (C) 2004 by the American College of Cardiology Foundation.