Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction (AMI). The Thrombolysis in Myocardial Infarction (TIMI) study grading scale for coronary perfusion has gained wide acceptance, but the significance of individual grades on clinical outcome has not been adequately tested. We hypothesized that optimal outcomes would be achieved only with early (and maintained) TIMI grade 3 (complete) perfusion compared with TIMI grade 2 (partial perfusion, previously classified as a reperfusion success) or grades 0 or 1 (occluded arteries). Five recent, angiographically controlled, prospectively performed studies of thrombolysis in AMI were identified, representing 3,969 patients. Odds ratios for mortality by early perfusion grades were calculated using the Mantel-Haenszel test and combined in a weighted fashion. Results for selected clinical and laboratory outcomes by patency grade were also assessed. Overall, mortality averaged 8.8% for TIMI grade 0/1, 7.0% for grade 2, and 3.7% for grade 3 perfusion. The odds ratio (OR) for early mortality was substantially reduced for grade 3 versus <3 perfusion (OR = 0.45, confidence interval [CI] 0.34 to 0.61, p <0.0001). In pairwise comparisons, grade 3 was clearly superior to grade 2 (OR = 0.54, CI) 0.37 to 0.78, p = 0.001) as well as grades 0/1 (OR = 0.41, CI 0.30 to 0.56, p <0.0001). Acute and convalescent ejection fraction, regional wall motion, time to enzyme peaks (creatine kinase [CK], creatine kinase myocardial bond [CK-MB]), peak enzyme levels [CK, lactate dehydrogenase [LDH], LDH-1), and risk of heart failure were each significantly less in patients achieving grade 3 than grade 2 (or lower grades) perfusion. Results were observed despite the frequent use of interventions after angiography. This meta-analysis demonstrates that early and complete (grade 3) flow is associated with superior survival and clinical outcome; grade 2 perfusion results in an inferior outcome, closer to that of an occluded than an open artery. The goal of reperfusion strategies should be early and maintained TIMI grade 3 perfusion.