Background: Bivalirudin has been shown to be safe and effective during percutaneous coronary interventions (PCI) of native coronary arteries in the REPLACE 2 trial. The safety of bivalirudin during PCIs in heart transplant patients is not known. Methods: Heart transplant patients who had undergone PCI of de novo lesions and received bivalirudin during the procedure were included in the study. Medical records were reviewed for the occurrence of death, myocardial infarction, target vessel revascularization or major bleeding up to 30 days after discharge. The results were compared with the REPLACE 2 trial and with a control group of heart transplant recipients who received heparin during their procedures. Results: There were 51 separate PCIs performed in 30 patients in the study group. The mean age was 56 ± 12 years and 6 (20%) were women. The control group consisted of 24 patients who had undergone 35 PCIs. There were no deaths, myocardial infarctions or target vessel revascularization during the follow-up period in the study group. The combined endpoint of death, myocardial infaretions, target vessel revascularization and major bleeding requiring two or more units of packed red blood cells occurred in 2 (3.9%) patients compared to 275 (9.2%) Patients in the REPLACE 2 trial (p = 0.195) and 5 (14.3%) in the control group (p = 0.115). Conclusion: Bivalirudin is a safe antithrombotic medication to use during elective PCI in heart transplant patients with cardiac allograft vasculopathy. Copyright © 2007 Via Medica.