The purpose of this study was to determine patient characteristics that are a priori predictors of early infarct related artery patency following thrombolytic therapy, and to provide a paradigm which may identify patients who would be most likely to achieve restoration of normal (TIMI 3) coronary flow in response to thrombolytic therapy. Restoration of infarct-related artery perfusion in acute myocardial infarction is necessary for preservation of ventricular function and mortality reduction. Clinical variables that are a priori predictors of early patency with currently available thrombolytic regimens have not been fully characterized. The probability of early infarct-related artery patency (TIMI 3 flow) was determined by multivariable logistic regression. We determined a reduced (parsimonious) model for predicting early (90 min) infarct-related artery patency (TIMI grade 3) based on data from 1,030 patients in the GUSTO-I Angiographic study. Predictors of 90 min TIMI 3 flow are use of an accelerated t-PA regimen (vs. streptokinase containing regimens) (chi2=39.1; p < or = 0.0001), infarct related artery (RCA/Lcx vs. LAD) (chi2=12.7; p=0.0004), body weight (chi2=10.3; p=0.001) and history of smoking (chi2=7.4; p=0.007). Time from symptom onset to treatment was not significant (p=0.71). The efficacy of currently available thrombolytic regimens is chiefly dependent on choice of thrombolytic regimen, body weight, infarct-related coronary artery and smoking history. Clinical variables alone correctly predict a priori TIMI 3 flow in the infarct-related artery 64% of the time. Patients with body weights greater than 85 kg are at a significant disadvantage with regard to achieving successful thrombolysis compared to those with lesser body weights.