Background: Cardiac allograft vasculopathy (CAV) constitutes a primary cause of death after heart transplantation. Balloon angioplasty and bare metal stents have been used for revascularization but they are associated with a high risk of re-stenosis. Limited data have shown favorable results with drug-eluting stents (DES). This study examines the rate of re-stenosis for DES in CAV as well as predictors for its occurrence. Methods: Cardiac transplant patients who received at least one DES for a previously untreated coronary lesion were included. These patients were retrospectively followed until February 2007. Re-stenosis was defined as ≥50% lumen diameter narrowing on coronary angiography at the site of the DES. Results: During the study period, 35 patients underwent percutaneous coronary intervention (PCI) on a total of 84 de novo lesions. The mean follow-up was 22 ± 14 months. Twenty-six (31%) lesions developed re-stenosis during follow-up. Re-stenosis rates were 18%, 21% and 26% at 6, 9 and 12 months, respectively. Predictors of re-stenosis included non-white race, ischemic etiology, intervention precipitated by symptoms and severe stenosis (≥90% stenosis) of the target lesion. Conclusions: Use of DES has a favorable outcome when used in heart transplant patients for the treatment of CAV. An aggressive strategy for the treatment of CAV using DES may provide good long-term outcome compared with other available therapies.