Thrombolytic therapy or intense anticoagulation during percutaneous transluminal coronary revascularization (PTCR) increases the risk of vascular access site complications. This study evaluated the association of abciximab, a glycoprotein IIb/IIIa receptor blocker, with vascular access site complications after PTCR. Of 2,058 patients who underwent PTCR in the Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) trial, major vascular access site bleeding (a drop in hematocrit > 15%), minor vascular access site bleeding (> 10% drop), or surgical repair of the access site occurred in 5%, 12%, and 1.4% of all patients, respectively. Minor and/or major bleeding or surgery occurred in 21.8% of abciximab patients, compared with 9.1% of placebo patients (p <0.001). Logistic regression analysis identified these predictors of minor and/or major bleeding and/or surgical repair, in descending order of importance: abciximab therapy, acute myocardial infarction at enrollment, high baseline hematocrit, time in catheterization laboratory, heavier weight, female gender, maximum in catherization laboratory activated clotting time, sheath size, and age (all p <0.05). Vascular access site complications increased median post-PTCR length of stay from 2 days (no bleeding) to 3 days (minor bleeding) and 6 days (major bleeding). Site-to-site variation in vascular access site complications varied sixfold. Analyses of subsequent studies of PTCR with abciximab will determine whether discontinuing heparin and removing sheaths early after PTCR reduces the risk of vascular access site complications.