Incidence and significance of pericardial effusion in patients with acute myocardial infarction (AMI) have not been established. To evaluate these issues, we studied prospectively 138 consecutive patients with AMI. An echocardiogram was obtained in each 1, 3, and 10 days and 3 and 6 months after admission. Fifty four patients with unstable angina and 57 without heart disease were studied as controls. Echocardiographic diagnostic criteria of pericardial effusion were established from 33 additional patients undergoing surgery. Pericardial effusion was found in 28% of patients with AMI. Twenty-five percent of patients with AMI had pericardial effusion on the third day, vs 8% of patients with unstable angina (p < .02) and 5% of patients without heart disease (p < .01). At 1, 3, and 10 days and 3 and 6 months prevalence of pericardial effusion was 17%, 25%, 21%, 1 1%, and 8%, respectively. There was no case of tamponade. Pericardial effusion was more common in anterior AMI (p < .02) and in patients with heart failure (p < .05) but it was not significantly associated with early pericarditis, peak creatine kinase-MB, the level of anticoagulation, or mortality. Thus, pericardial effusion is a common event in patients with AMI (incidence of 28%), but does not result in specific complications. The reabsorption rate of pericardial effusion is slow and, in our experience, mild or moderate pericardial effusion does not preclude heparin therapy.