Multivessel percutaneous coronary intervention (PCI) early after acute myocardial infarction (AMI) is discouraged because of the potential for increased complications. However, with recent advances in PCI, the safety and long-term outcomes of multivessel PCI are unknown. We evaluated the outcomes of multivessel PCI early after AMI (ST-elevation and non-ST-elevation AMI). We identified all patients who had multivessel disease and underwent PCI within 7 days after an AMI from 1997 to 2002. Clinical outcomes were compared between patients who underwent multivessel PCI (n = 239) and patients who underwent treatment of the infarct-related artery alone (n = 1,145). The primary end point was cumulative survival at 6, 12, and 36 months. Secondary end points included a composite of mortality, recurrent infarction, coronary artery bypass graft, or target vessel revascularization at the same time points. There were 138 deaths and 351 occurrences of the composite end point during follow-up. The multivessel PCI group had a significantly higher prevalence of adverse prognostic indicators. Despite this, observed event rates were similar between the multivessel PCI and 1-vessel PCI groups. The Kaplan-Meier estimated 1-year survival was 0.91 (95% confidence interval [CI] 0.87 to 0.95) for the multivessel PCI group and 0.93 (95% CI 0.92 to 0.95) for the 1-vessel PCI group (p = 0.43). Similarly, 1-year survival free of recurrent infarction and target vessel revascularization rates were similar between the 2 groups: multivessel PCI 0.78 (95% CI 0.73 to 0.84) and 1-vessel PCI 0.78 (95% CI 0.75 to 0.81). Multivessel PCI in patients with multivessel coronary artery disease after AMI compared with 1-vessel PCI was not associated with an excess risk of death or of combined death, myocardial infarction, coronary artery bypass graft, or target vessel revascularization.