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With excellent short-term survival in liver transplantation (LT), we now focus on long-term outcome and report the first European single-center 20-year survival data. Three hundred thirty-seven LT were performed in 313 patients (09/88–12/92). Impact on long-term outcome was studied and a comparison to life expectancy of matched normal population was performed. A detailed analysis of 20-years follow-up concerning overweight (HBMI), hypertension (HTN), diabetes (HGL), hyperlipidemia (HLIP) and moderately or severely impaired renal function (MIRF, SIRF) is presented. Patient and graft survival at 1, 10, 20 years were 88.4%, 72.7%, 52.5% and 83.7%, 64.7% and 46.6%, respectively. Excluding 1-year mortality, survival in the elderly LT recipients was similar to normal population. Primary indication (p < 0.001), age (p < 0.001), gender (p = 0.017), impaired renal function at 6 months (p < 0.001) and retransplantation (p = 0.034) had significant impact on patient survival. Recurrent disease (21.3%), infection (20.6%) and de novo malignancy (19.9%) were the most common causes of death. Prevalence of HTN (57.3–85.2%, p < 0.001), MIRF (41.8–55.2%, p = 0.01) and HBMI (33.2–45%, p = 0.014) increased throughout follow-up, while prevalence of HLIP (78.0–47.6%, p < 0.001) declined. LT has conquered many barriers to achieve these outstanding long-term results. However, much work is needed to combat recurrent disease and side effects of immunosuppression (IS).This paper reports on European single-center 20-year survival data after liver transplantation with a detailed analysis of impact on long-term outcome, causes of death, comorbidities and life expectancy in comparison to gender and age-matched normal population.