OBJECTIVE: To assess the short- and long-term costs and clinical and quality of life outcomes with the use of streptokinase (SK) vs tissue plasminogen activator (tPA) for acute myocardial infarction (MI), DESIGN: A decision analysis model, PATIENTS: Patients with acute MI who were candidates for thrombolytic therapy and who presented within six hours of symptom onset, MEASUREMENTS: 30-day and one-year mortality, impacts of disabling and nondisabling stroke, reinfarction, hemorrhage, hypotension, anaphylaxis, and long-term medical costs, RESULTS: Using 30-day mortality data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, the baseline analysis yielded an incremental cost-effectiveness for tPA of $30,300 per additional quality-adjusted life year [QALY] gained, compared with SK, Using one-year mortality data from the GUSTO trial, the analysis yielded an incremental cost-effectiveness for tPA of $27,400 per additional QALY, compared with SK, The incremental cost-effectiveness of tPA over SK was sensitive to the difference in mortality seen with the two agents, exceeding $100,000 per QALY, for a relative survival advantage of approximately one-third that seen in the GUSTO trial, The incremental cost per QALY of tPA remained under $60,000 if the survival benefit was half that seen in the GUSTO trial, The cost-effectiveness of tPA declined with a shorter projected life expectancy following MI and for inferior [vs anterior] wall infarction, The analysis was modestly sensitive to the costs of the thrombolytic agents, CONCLUSIONS: In spite of its higher cost relative to SK, tPA is a cost-effective therapy for Mi under a wide range of assumptions regarding clinical outcomes and costs, KEY WORDS: thrombolytic therapy; cost-effectiveness analysis; streptokinase; tissue plasminogen activator; myocardial infarction.