Abstract Objectives. The Heart Transplantation Center, Aarhus University Hospital, Skejby, now has 20 years' experience with heart transplantation (HTX). This study aims to evaluate long-term outcome after HTX including incidences of cancer and severe renal dysfunction. Design. Outcomes were reviewed using the transplant database of our department, the Scandiatransplant database, hospital medical records, and national database of biopsies. Results. From December 31, 1992 to February 27, 2013, a total of 258 patients underwent index HTX. Survival for the whole patient cohort at 1 month and 1 year was 95% and 88%. Long-term survival estimates of 5, 10, 15, and 20 years were 80%, 70%, 55%, and 40%, respectively. Median survival time was 15.6 years. Significant improvement in survival was observed from the 1992-1998 vs. 1999-2005 era and the 1992-1998 vs. the 2006-2012 era. Three patients (1%) underwent renal transplantation, and 29 patients (11%) developed severe renal dysfunction requiring dialysis. Sixty-four (25%) patients developed cancer, with skin cancer being most common. Conclusion. HTX is an excellent treatment for selected patients with end-stage heart failure. The prognosis has improved in the latest transplantation eras. With balanced immunosuppressive treatment, severe renal dysfunction and cancer can be limited to an acceptable level.