Infarct artery stenting with adjunctive abciximab therapy is widely used treatment for patients with acute myocardial infarction (AMI). However, bleeding complications have been associated with a worse clinical outcome. Randomized trials in elective patients have shown that postprocedural protamine administration is safe and associated with a significant reduction in bleeding complications. The aim of the current study was to evaluate in STEMI patients undergoing primary percutaneous coronary intervention (PCI) with abciximab and stenting whether immediate reversal of anticoagulation by protamine is safe and associated with a reduction in the occurrence of bleeding complications. From January 2004 to June 2005, 254 patients with STEMI had immediate reversal of anticoagulation by protamine administration after infarct artery stenting and received abciximab therapy without heparin infusion (Group 1). These patients were compared with a control group of 265 patients (June 2002-December 2003) treated with the standard heparin therapy: bolus in order to achieve an activated coagulation time of 250-300 s during PCI plus 12-h infusion (7 UI/kg/h; Group 2). We excluded patients undergoing IABP implantation. The two groups were similar in all baseline characteristics. There were no differences in in-hospital mortality, reinfarction, urgent target vessel revascularization, stroke or acute or subacute stent thrombosis, while Group 1 patients showed a lower incidence of major bleeding complications (ACUITY scale: 1.1 vs. 4.0%, P = 0.035) and a shorter length of hospital stay (3.5 ± 1.7 vs. 4.0 ± 1.6 days, P = 0.002) as compared with heparin treated patients. Among patients undergoing primary stenting with abciximab administration, immediate post-PCI reversal anticoagulation by protamine without associated heparin infusion is safe and associated with a significant reduction in major bleeding complications.