To evaluate the clinical incidence and outcomes of patients with pericarditis after thrombolytic therapy, 810 patients were prospectively studied during acute myocardial infarction (AMI). Pericarditis was defined as the presence of a pericardial friction rub during the hospital course. Only 5% of patients developed a rub during AMI, a low percent compared with that in the prethrombolytic era. A pericardial friction rub more often occurred in the setting of an anterior wall AMI. Patients with, compared to those without, a pericardial friction rub had lower ejection fractions (45 vs 51%, p = 0.002); worse regional left ventricular function (-3.2 vs 2.7, standard deviation per chord); higher in-hospital mortality (15 vs 6%, p = 0.056); a higher frequency of power failure (83 vs 57%); a higher frequency of anterior wall location of the AMI (53% of cases, p = 0.002); and a higher frequency of 3-vessel disease. Therefore, although the frequency of a pericardial friction rub was low (5%) compared with that in the prethrombolytic era, its occurrence denotes more extensive myocardial damage with a worse clinical outcome. Perhaps with successful reperfusion of the infarct-related vessel, transmural myocardial necrosis is prevented and with it the development of pericarditis. Cardiac tamponade did not occur clinically in any patient who developed a pericardial friction rub.