In the Primary Angioplasty in Myocardial Infarction trial, 395 patients with acute myocardial infarction (AMI) were prospectively randomized to tissue plasminogen activator (tPA) or primary percutaneous transluminal coronary angioplasty (PTCA). In 138 patients with anterior wall AMI, in-hospital mortality was significantly reduced by treatment with PTCA compared with tPA (1.4% vs 11.9%, p = 0.01). PTCA also resulted in lower rates of death or reinfarction (1.4% vs 18.0%, p = 0.0009), recurrent myocardial ischemia (11.3% vs 28.4%, p = 0.01), and stroke (0.0% vs 6.0%, p = 0.037) in anterior wall AMI. The independent beneficial effect of treatment with primary PTCA rather than tPA in anterior wall AMI was confirmed by multivariate analysis and interaction testing. The in-hospital mortality of 257 patients with nonanterior wall AMI was similar after PTCA and tPA (3.2% vs 3.8%, p = 0.82). Compared with tPA, however, primary PTCA resulted in a markedly lower rate of recurrent myocardial ischemia (9.7% vs 27.8%, p = 0.0002), fewer unscheduled catheterization and revascularization procedures, and a shorter hospital stay (7.0 vs 8.6 days, p = 0.01) in nonanterior wall AMI. Thus, compared with tPA, primary PTCA in patients with anterior wall AMI results in significantly improved survival, with lower rates of stroke, reinfarction, and recurrent myocardial ischemia. In nonanterior wall AMI, treatment with PTCA and tPA results in similar early mortality, although PTCA-treated patients have a more stable hospital course characterized by reduced recurrent ischemia, fewer subsequent invasive procedures, and earlier discharge.