Over the past decades donor and recipient characteristics and medical management of heart transplantation (HT) patients have changed markedly. We studied the impact of these changes on long-term clinical outcome. Data of all consecutive HT recipients in our center have been collected prospectively. Cohort A (n=353) was defined as the adult pts transplanted between 1984 and 1999 and was compared with cohort B (n=227) transplanted between 2000 and 2013. Compared with cohort A, recipients in cohort B had older donors (mean age 29 vs. 43years, donors aged >50year: 2% vs. 33%, respectively). Survival at 1 and 10years in cohort A vs. B was 89% vs. 86% and 53% vs. 68%, respectively (P=0.02). Cohort B pts were treated more often with tacrolimus-based immunosuppression (77% vs. 22%; P=<0.0001) and early statins post-HT (88% vs. 18%; P=0.0001), while renal function was better conserved at 5 and 10years (P=0.001 and 0.02). Multivariate analysis showed significant reduction in 10-year mortality with tacrolimus-based immunosuppression (HR 0.27 and 95% CI 0.17-0.42), hypertension post-HT (HR 0.5, 95% CI 0.36-0.72), and revascularization (HR 0.28, 95% CI 0.15-0.52). In spite of the use of much older donors, the long-term outcome after HT has improved considerably in the last decade, probably due to the introduction of newer treatment modalities.