We evaluated the utility of a routine postprocedure course of unfractionated heparin after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in patients not receiving glycoprotein IIb/IIIa inhibitors. In the CADILLAC study, 2,082 patients with AMI who underwent primary PCI were randomized to receive stents versus percutaneous transluminal coronary angioplasty (PTCA), each with or without abciximab. In a subset of 976 patients who did not receive abciximab, we compared outcomes of patients who received postprocedural heparin (n = 758; 78%; median duration 2 days) with those who did not. In 421 patients treated with PTCA, postprocedural heparin use was associated with lower in-hospital major adverse cardiac events (MACEs; 5.3% vs 11.4%, p = 0.069), 1-year MACEs (22% vs 31%, p = 0.08), and decreased in-hospital moderate/severe bleeding (2.3% vs 8.9%, p = 0.01). By multivariate analyses, heparin use correlated with freedom from in-hospital and 1-year MACEs in patients after PTCA. In contrast, in 555 patients who underwent stenting, postprocedural heparin use was associated with increased bleeding and hospitalization costs without a decrease in early or late MACEs. In conclusion, in patients with AMI treated with coronary stenting without glycoprotein IIb/IIIa inhibitors, routine postprocedural heparin was not associated with any significant benefits and may be safely omitted. However, in a subset of patients treated with PTCA, postprocedural heparin use was independently associated with fewer in-hospital and 1-year MACEs.