Late morbidity and death as a result of progressive coronary vascular obliteration remains a major unsolved problem after orthotopic heart transplantation. Various percutaneous catheter intervention (PCI) methods have been used to treat transplant coronary artery disease (CAD), but few reports have assessed the longitudinal results of these procedures. Of 1,440 cardiac transplant patients at University of California, Los Angeles, Medical Center, treated between 1984 and 2004, 65 patients who had undergone orthotopic heart transplantation underwent PCI on a total of 156 coronary artery lesions because of transplant CAD between July 1993 and August 2004. The procedural success rate was 93%. Angiographic follow-up was available for 42 patients and 101 lesions 9.5 +/- 5.8 months after PCI. The global restenosis rate was 36%. Multivariate analysis was used to assess 49 clinical, angiographic, and immunologic variables per lesion. The use of a cutting balloon increased the risk of restenosis (odds ratio 11.5, p <0.01) and the use of stents decreased the risk of restenosis (odds ratio 0.34, p <0.05) compared with other PCI methods. The restenosis rate with drug-eluting stents was 19%, lower than that with bare metal stents (31%). Of the 65 patients, 20 (31%) died within 1.9 +/- 1.8 years after PCI. The actuarial survival rate was 56% at 5 years after the first PCI. In conclusion, although the restenosis rate after PCI was higher than that in nontransplant patients with CAD, the immediate and long-term results were acceptable in this high-risk population. Despite the intense inflammation associated with transplant CAD, drug-eluting stents appeared to reduce the occurrence of restenosis. Compared with historical controls, PCI may also improve the actuarial survival rate of patients undergoing orthotopic heart transplantation.