Bivalirudin is a synthetic analog of hirudin that binds reversibly to thrombin. It belongs to a group of anticoagulants that act as direct thrombin inhibitors and whose effect is highly predictable. The aim of this review was to answer the question: How does the efficacy and safety of bivalirudin in patients with non-ST-elevation acute coronary syndrome compare with that of the combination of (unfractionated or low-molecular-weight) heparin and a glycoprotein-IIb/IIIa inhibitor? The two treatment strategies have been compared in two studies (i.e. ACUITY and REPLACE-2), both of which had a complex design and were difficult to interpret. These studies demonstrated that the two treatment strategies had similar efficacy in terms of preventing cardiac events and that fewer hemorrhagic complications occurred in the groups assigned to bivalirudin. We carried out a thorough analysis of the data available and their limitations, the results of which can serve as a basis for implementing one or other strategy in treatment protocols for non-ST-elevation acute coronary syndrome.