Transplant allograft vasculopathy (TAV) was a leading cause of death in cardiac transplant recipients after the first year of transplantation. Whether drug-eluting stents (DESs) performed better than bare-metal stents (BMSs) for the treatment of patients with discrete epicardial stenosis was unknown. The aim was to determine the safety and efficacy of DESs compared with BMSs in the treatment of patients with TAV. Outcomes of 32 patients sequentially treated using DESs for TAV were retrospectively reviewed and compared with a historic cohort of 35 patients treated sequentially with BMSs for TAV. Patients treated with DESs were also compared with age- and gender-matched cardiac transplant controls to determine differences in survival. After adjustment for baseline risk factors, there was no difference in 1-year survival between patients treated with DESs or BMSs for TAV. Restenosis rates at 1 year were 49% in lesions treated using BMSs and 19% in those treated using DESs. Compared with an age- and gender-matched control group of cardiac transplant patients who did not have discrete obstructive epicardial TAV, patients who required treatment with DESs for epicardial obstructive disease had significantly worse survival. In conclusion, treatment of patients with TAV with DESs did not seem to alter the natural deleterious history of this disease process.