Studies have shown poor prognostic implications of anemia in patients with myocardial infarction (MI) and in patients undergoing percutaneous coronary intervention (PCI). The impact of blood transfusion in these populations remains controversial. The objective of this study was to examine the effect of transfusion on in-hospital mortality in anemic patients undergoing PCI for MI. Data from 67,051 PCIs (June 1, 1997 to January 31, 2004) were prospectively collected in a multicenter registry (Blue Cross Blue Shield of Michigan Cardiovascular Consortium). Of these, 4,623 patients who were classified as anemic according to the World Health Organization criteria underwent PCI within 7 days of presentation with acute MI. A propensity score for being transfused was estimated for each patient, and propensity matching and a prediction model for in-hospital death were developed. The average age was 67.8 years, 57.7% of patients were men, and 22.3% of patients received a transfusion during hospitalization. Transfused patients, compared to nontransfused patients, were more likely to be older, female, have lower preprocedure hemoglobin levels, more comorbidities, and a higher unadjusted in-hospital mortality rate (14.52% vs. 3.01%, p < 0.0001). After adjustment for comorbidities and propensity for transfusion, blood transfusion was associated with a higher risk of in-hospital mortality (adjusted odds ratio = 2.02, 95% confidence interval 1.47-2.79, p < 0.0001). In anemic patients undergoing PCI for MI, transfusion was associated with an increased crude and adjusted rate of in-hospital mortality. A randomized controlled trial is needed to determine the value of transfusion and the ideal transfusion criteria.