Reperfusion therapy for acute myocardial infarction is one of the most thoroughly studied treatments in all of medicine. The GISSI-1 and ISIS-2 megatrials definitively established the superiority of intravenous streptokinase over conservative care for this condition. Tissue plasminogen activator (t-PA) was introduced with the expectation that it would be substantially more effective than streptokinase. It was also priced at approximately $2000, more than streptokinase, a cost differential that set the stage for a heated and often contentious debate about the added value of t-PA. Two European trials, GISSI-2 and ISIS-3, subsequently found that t-PA and streptokinase provided equivalent health outcomes. It was in this setting that the GUSTO trial was conceived. The major result of GUSTO was the finding that accelerated t-PA saved 11 additional lives per 1000 patients treated. In order to address the question of whether the extra benefits of t-PA were worth its significant extra costs, we performed a detailed cost-effectiveness analysis using the empirical data from the GUSTO-I trial. The net incremental cost for each patient shifted from streptokinase to t-PA in GUSTO-I was;dollar;2845. The majority of this difference was attributable to the difference in the cost of the thrombolytic agents. Survival modeling showed that accelerated t-PA added 0.14 undiscounted years per patient or, alternatively, that each of the 11 extra survivors per 1000 patients shifted from streptokinase to t-PA lived an average of 14 additional years. The incremental cost-effectiveness ratio for routine substitution of t-PA for streptokinase was;dollar;32,678 per added life year. Compared with standard benchmarks, our analysis shows that routine substitution of t-PA for streptokinase is "economically attractive." Subgroups analysis further showed that cost-effectiveness ratios were most favorable in older patients and in anterior myocardial infarctions. Perhaps one of the most important results of the GUSTO-I trial is that it demonstrates that an expensive new biotechnology therapy can have a favorable economic profile if it produces sufficient additional health benefits.