Thrombocytopenia that develops after percutaneous coronary intervention (PCI) may result in hemorrhagic complications, requirement for blood product transfusions, and potentially thrombotic or ischemic complications. The incidence and prognostic significance of thrombocytopenia, in patients with acute myocardial infarction (AMI) who undergo primary PCI have not been evaluated. In the CADILLAC trial 2,082 patients who had AMI within 12 hours of onset without shock were prospectively randomized to receive balloon angioplasty with or without abciximab versus stenting with or without abciximab. Acquired thrombocytopenia, defined as a nadir platelet count <100 x 10(9)/L in patients who did not have baseline thrombocytopenia, developed in 50 of 1,975 qualifying patients (2.5%) after primary PCI. By multivariate analysis, acquired thrombocytopenia developed more frequently in patients who had non-insulin-requiring diabetes mellitus (odds ratio 3.88 [OR], p = 0.0002), previous statin administration (OR 3.28, p = 0.002), and use of abciximab (OR 2.06, p = 0.02) and less frequently in patients who had previous aspirin use (OR 0.26, p = 0.002), a higher baseline platelet count (OR 1.20, p < 0.0001), and greater body mass index (OR 0.90, p = 0.006). Patients who developed thrombocytopenia versus those who did not had higher in-hospital rates of major hemorrhagic complications (10.0% vs 2.7%, p = 0.01), greater requirement for blood transfusions (10.0% vs 3.9%, p = 0.05), longer hospital stay (median 4.8 vs 3.6 days, p = 0.008), and increased costs (median dollar 14,466 vs dollar 11,629, p = 0.001). All-cause mortality was markedly increased at 30 days (8.0% vs 1.6%, p = 0.0008) and at 1 year (10.0% vs 3.9%, p = 0.03) in patients who developed thrombocytopenia. In conclusion, thrombocytopenia that develops after primary PCI for AMI, although uncommon, is associated with increased hemorrhagic complications and decreased survival.