To determine whether pharmacologic reperfusion to Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow during acute myocardial infarction confers the same clinical benefit as restoration of TIMI 3 flow, in-hospital clinical and angiographic outcomes in 1,229 patients prospectively enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction trials were analyzed. Patients were treated with intravenous tissue plasminogen activator or urokinase, or both. Angiography of the infarct-related artery 90 minutes after initiation of thrombolytic therapy demonstrated TIMI grades 0, 1, 2, or 3 flow in 20%, 7%, 17%, and 55% of vessels, respectively. Rescue or adjunctive coronary angioplasty was performed in 80%, 27%, and 16% of patients with TIMI 0/1, 2, or 3 flow, respectively. Predischarge angiography was performed in 963 patients. A significant gradient of increasing mortality was seen in patients with lower TIMI flow (4.3%, 6.1%, and 10.1% with TIMI 3, 2, and 0/1 flow, respectively, p = 0.002). The incidence of congestive heart failure and recurrent ischemia was significantly higher in patients with TIMI 2 than with TIMI 3 perfusion (26% vs 19% for heart failure, p = 0.03; 23% vs 17% for recurrent ischemia, p = 0.05). Acute left ventricular ejection fraction and infarct zone regional wall motion were also significantly improved in patients with TIMI 3 than with TIMI 2 flow, with trends toward better improvement in global and regional function in the TIMI 3 group. These findings were not affected by the use of acute coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)