Although several studies have previously reported on the efficacy of percutaneous coro-nary intervention (PCI) with first-generation drug-eluting stents (DES) in heart transplant patients with cardiac allograft vasculopathy, few data regarding new-generation DES are currently available. We sought to compare the efficacy of new-generation versus first-gen-eration DES in 90 consecutive patients with heart transplant (113 de novo coronary lesions) who underwent urgent or elective PCI with first-generation (28 patients) or new-generation (62 patients) DES. For each patient, the severity of cardiac allograft vasculop-athy and postprocedural extent of revascularization were quantified calculating baseline and residual SYNTAX score, respectively. The primary end point was a composite of major adverse cardiac events-myocardial infarction, cardiovascular death, or target ves-sel revascularization-at 3 years. Overall, the median baseline SYNTAX score was 8 (5 to 15), and a total number of stents per patient of 1.6 +/- 0.9 was implanted. Post-PCI residual SYNTAX score was 1.5 (0 to 4), with 13 patients having a score >8. At 3 years, the Kaplan -Meier estimate of freedom from major adverse cardiac events was 64%, with no differ-ences between first-generation and new-generation DES groups (log-rank test p = 0.269). Nevertheless, patients treated with new-generation DES experienced a lower rate of target vessel revascularization (15% vs 31%, log-rank test p = 0.058). In the multivariate Cox regression analysis, a post-PCI residual SYNTAX score >8 (hazard ratio 2.37, confidence interval 0.98 to 5.73, p = 0.054) was identified as an independent predictor of the primary end point.