Little comparative data exist for glycoprotein IIb/IIIa inhibitors in acute coronary syndromes (ACS). Two hundred twenty-eight patients were studied: 114 received tirofiban (TI) and 114 received abciximab (AB) for either unstable angina (UA) or myocardial infarction (MI). All patients received aspirin, heparin, and ticlopidine or clopidogrel. Baseline characteristics were similar between the 2 groups for admitting diagnosis (UA vs MI), age, gender, ejection fraction, diabetes mellitus, prior coronary artery disease, prior myocardial infarction (MI), prior bypass surgery, hypertension, congestive heart failure, hyperlipidemia, MI type (Q vs non-Q), or location. Drug administration time (mean) was 13 hours (AB) and 24 hours (TI). All AB was administered in the catheterization laboratory as compared to TI (34% in laboratory and 66% before laboratory). More AB patients received angioplasty or stent (92% vs 80%, p = 0.008) while more TI patients had CABG (10% vs 3%, p = 0.027). In-hospital complications including death, MI, urgent revascularization, cerebrovascular accidents or transient ischemic attacks, and access site bleeding were similar (p = NS). Multivariate predictors of events (odds ratios) were prior coronary artery bypass graft (2.3), diabetes (1.7), and prior percutaneous transluminal coronary angioplasty (1.7), but not the agent used. Over a mean follow-up of 13 months, the individual endpoints of death, MI, revascularization, or hospitalization were similar for both groups. The AB patients had improved freedom from revascularization (100% vs 81%, p = 0.015) in an emergent setting and TI patients had improved freedom from revascularization (93% vs 77%, p = 0.038) with elective procedures. Tirofiban and abciximab appear effective and safe when used for ACS when recommended dosing and precautions are followed. Major adverse outcomes are rare and bleeding complications uncommon.