Our purpose was to evaluate the outcomes of patients with prior coronary angioplasty who underwent thrombolysis for new acute myocardial infarction (AMI) in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial. Baseline characteristics and clinical outcomes were compared between patients with (n = 1,647) and without (n = 39,150) previous angioplasty. The relations among prior angioplasty, clinical outcomes, and treatment effects were examined with logistic regression modeling. Patients with previous angioplasty tended to be younger and presented sooner after symptom onset, but had more multivessel disease and lower ejection fractions. Unadjusted mortality was significantly lower in the prior-angioplasty group at 24 hours (1.8% vs 2.7%, p = 0.03) and 30 days (5.6% vs 7.0%, p = 0.036). Although most of the survival advantage was due to low-risk characteristics in this group (lower age and heart rate and fewer anterior wall AMIs), prior angioplasty remained a weak but independent predictor of survival. Recurrent ischemia and reinfarction occurred more often in the prior-angioplasty group, as did bypass surgery (12.2% vs 8.5%) and repeat angioplasty (34.5% vs 21.4%). Patients with prior angioplasty and prior AMI had lower 30-day mortality than those with prior infarction alone (6.3% vs 12.6%, p < 0.01). Treatment effects on 30-day mortality were similar among patients with prior angioplasty (odds ratio 1.2 for accelerated tissue-plasminogen activator v. combined streptokinase arms, 95% confidence interval 0.73 to 1.9). Patients with prior angioplasty who present with AMI have fewer in-hospital adverse events and lower 30-day mortality than those without such a history.