Objectives. We sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI). Background. Primary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group. Methods. Data from NRMI-2 were reviewed. Results. From June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lyticineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In- hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic- eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA). Conclusions. These findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.