BACKGROUND Over the past 2 decades, there have been many medical advances in the field of liver transplantation. We conducted this study to evaluate the changes in liver transplantation over the last 2 decades. MATERIAL AND METHODS Three hundred cases of liver transplantation encountered between 1997 and 2019 in Nagasaki University Hospital were divided into 3 groups: Era 1 (cases no. 1-100), Era 2 (cases no. 101-200), and Era 3 (cases no. 201-300). Several items were compared among the groups. RESULTS There were no cases of deceased-donor liver transplantation in Era 1, 1 case in Era 2, and 12 cases in Era 3. The proportion of virus-related disease was significantly lower in Era 3 compared to other eras. In contrast, the proportion of alcoholic liver cirrhosis was significantly higher in Era 3 (27%) than Era 1 (7%) and Era 2 (10%) (P<0.01). In Era 1, the right lobe was selected most frequently, but in Eras 2 and 3, the left lobe was more frequently selected. CONCLUSIONS The evolution of the treatment and the transplant system in Japan is clearly reflected in the indications and types of donors for liver transplantation, even at a single center in Japan.