During coronary angioplasty, the association of platelet inhibitors and antithrombin agents is required to prevent myocardial infarction. Bivalirudine, a synthetic direct thrombin inhibitor, has been widely validated in this context and has shown its efficacy and safety in several comparative studies. It is officially recommended as a replacement of NFH and LMWH associated or not with anti-GPIIb/IIIa agents because at comparable efficacy it causes fewer bleeding complications. In acute coronary syndromes without ST elevation, anti GPIIb/IIIa agents reduce angioplasty-related complications and mortality, especially in high risk patients in salvage situations. In the REPLACE-2 trial the clinical efficacy of bivalirudine (associated only when necessary with anti-GPIIb/IIIa agents) was no less than that of NFH associated systematically with anti-GPIIb/IIIa agents at the time of intervention. The incidents of serious adverse events at 30 days (death, infarctus, emergency revascularisation, major bleeding) in the bivalirudine group was 9.2% versus 10.2% in the NFH group. In a retrospective analysis, these results did not seem to be influenced by the prior administration of clopidogrel. Finally, the one year follow-up results showed a lower mortality in patients treated with bivalirudine (1.9% versus 2.5%), essentially in the high risk sub-groups such as the elderly, the diabetic or the renal failure patients. Clinical trials are underway (ACUITY) to study the interaction of anti GPIIb/IIIa agents with bivalirudine in the first hours of acute coronary syndromes and should confirm a major role of direct anti-thrombin drugs in the safety of angioplasty.