This study examined the incremental cost-effectiveness of extending clopidogrel therapy from one month to one year after percutaneous coronary intervention(PCI) in an unselected, heterogeneous patient population. Clinical trials suggest that prolonging clopidogrel therapy for up to one year after PCI reduces downstream cardiac events. However, clopidogrel therapy is costly and may increase bleeding risk. Using decision analysis, we compared the outcomes and cost of prolonging clopidogrel treatment from one month to one year after PCI with the alternative strategy of discontinuing therapy one month after the procedure. Event rates were based on 3,976 PCI patients who were treated between January 1999 and December 2001 at the Duke Medical Center and received no more than one month of clopidogrel after the procedure. Baseline characteristics and event rates were obtained from Duke clinical information systems. The effect of prolonged clopidogrel therapy on event rates was based on the Clopidogrel for the Reduction of Events During Observation(CREDO) trial per-protocol data. Unit costs and the effect of myocardial infarction(MI) on life expectancy were based on published sources. Extending clopidogrel therapy from one month to one year after PCI cost ＄879 per patient and reduced the risk of MI by 2.6%. Assuming MI decreases life expectancy by two years, prolonged therapy would cost ＄15,696 per year of life saved. Economic attractiveness of therapy varied with baseline risk, the effect of prolonged therapy on MI risk, and the price of clopidogrel. Prolonging clopidogrel therapy for one year after PCI is economically attractive, particularly in high-risk patients. This study examined the incremental cost-effectiveness of extending clopidogrel therapy from one month to one year after percutaneous coronary intervention (PCI) in an unselected, heterogeneous patient population. Clinical trials suggest that prolonging clopidogrel therapy for up to one year after PCI yet led cardiac events. However, clopidogrel therapy is costly and may increase bleeding risk. Using decision analysis, we compared the outcomes and cost of prolonging clopidogrel treatment from one month to one year after PCI. Rates were based on 3,976 PCI patients who were treated between January 1999 and December 2001 at the Duke Medical Center and received no more than one month of clopidogrel after the procedure. Baseline characteristics and event rates were obtained from Duke clinical information systems. The effect of prolonged clopidogrel therapy on event rates was based on the Clo pidogrel for the Reduction of Events During Observation (CREDO) trial per-protocol data. Unit costs and the effect of myocardial infarction (MI) on life expectancy were based on published sources. Extending clopidogrel therapy from one month to one year after PCI cost $ 879 per patient and reduced the risk of MI by 2.6%. Assuming MI decreases life expectancy by two years, prolonged therapy would cost $ 15,696 per year of life saved. Economic attractiveness of therapy varied with baseline risk, the effect of prolonged therapy on MI risk, and the price of clopidogrel. Prolonging clopidogrel therapy for one year after PCI is economically attractive, particularly in high-risk patients.