The incidence of minimal residual atherosclerotic coronary obstruction after successful intravenous thrombolytic therapy was evaluated in 799 patients with acute myocardial infarction. Minimal residual coronary obstruction (less than or equal to 50%) was observed on selective coronary angiography performed 90 min after initiation of thrombolytic therapy in 43 patients (5.5%). In 42 other patients (5.4%), a greater than 50% but less than 100% residual stenosis noted at 90 min demonstrated further resolution of obstruction to less than 50% at an angiographic follow-up study 7 to 10 days later. Patients with minimal residual coronary obstruction were significantly younger (52 +/- 10.7 versus 56.7 +/- 10 years; p = 0.002) and had less multivessel coronary disease (p less than 0.001), better initial left ventricular ejection fraction (54 +/- 12% versus 50.2 +/- 11.4%; p = 0.006) and a lower in-hospital mortality rate (1% versus 7%; p = 0.04) than did patients who had a significant (greater than 50%) residual coronary obstruction after intravenous thrombolysis. Long-term follow-up study of patients with a minimal coronary lesion (average 1.5 +/- 0.6 years) and those with significant residual stenosis (average 1.6 +/- 0.7 years) demonstrated that the incidence of death (2.4% in patients with minimal stenosis versus 3.5% in those with significant stenosis) and recurrent myocardial infarction (5% each) were similar in both groups. New strategies are needed to prevent coronary rethrombosis in patients with minimal atherosclerosis after thrombolytic therapy for acute myocardial infarction.