Bivalirudin is a synthetic 20 amino acid polypeptide that directly inhibits both fibrin-bound and soluble thrombin. In the randomized, open-label, multicentre HORIZONS-AMI trial in patients with ST-segment elevation myocardial infarction (STEMI) who were undergoing primary percutaneous coronary intervention (PCI), compared with unfractionated heparin (UFH) plus a glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin was associated with a significantly lower 30-day rate of net adverse clinical events that was largely due to the significantly lower 30-day rate of non-coronary-artery bypass grafting major bleeding. There was no significant between-group difference in the 30-day rate of major adverse cardiovascular events. These 30-day clinical outcomes were maintained at the 1- and 2-year follow-up. Bivalirudin, compared with UFH plus a GP IIb/IIIa inhibitor, was associated with lower short(30-day) and long- (1- and 2-year) term overall and cardiac mortality rates. Although there was an increased risk of acute stent thrombosis within 24 hours in recipients of bivalirudin compared with UFH plus a GP IIb/IIIa inhibitor, there was no significant between-group difference between 24 hours and 30 days, <= 30 days, <= 1 year or <= 2 years.