To evaluate outcome and quality of life (QoL) in ≥ 20 years survivors after heart transplantation. Patients surviving ≥ 20 years with a single graft were retrospectively reviewed. Heterotopic, multiorgan and retransplantations were excluded. QoL was evaluated using the SF-36 survey. Eight hundred and twenty-seven heart transplants were performed from 1981 to 1993, and among these, 131 (16%) patients survived ≥ 20 years; 98 (75%) were male and mean age at transplant was 43 ± 13 years. Conditional survival in these 20 years survivors was 74.1 ± 4.3% at 23 years and 60.9 ± 5.3% at 25 years (45 deaths, 34%). Forty-four (34%) patients suffered rejection ≥ 2R. Conditional survival free from rejection ≥ 2R was 68 ± 4.1% at 5 years and 66.4 ± 4.2% at 10 years. Thirty-five (27%) patients had cardiac allograft vasculopathy (CAV) grade 2-3. Conditional CAV-free survival was 76 ± 3.8% at 20 years and 72.1 ± 4% at 25. Sixty-nine (53%) patients developed malignancy, mostly skin cancers. Conditional malignancy-free survival was 53.5 ± 4.4% at 20 years and 45.2 ± 4.6% at 25 years. At latest follow-up, 24.0 ± 3.0 years after transplantation, mean left ventricular ejection fraction was 62 ± 11% and mean physical and mental scores were 57 ± 23 and 58 ± 21, respectively. Sixteen per cent of heart recipients survived ≥ 20 years with good ventricular performance and QoL. CAV and malignancies account for late morbidity and mortality.