Intrahepatic cholangiopathy is a life-threatening sequela of ABO-incompatible liver transplantation. We analyzed the clinical impact of pretransplant administration of mycophenolate mofetil in reducing intrahepatic cholangiopathy in ABO-incompatible liver transplantation. Patients who underwent living donor liver transplantation between 2010 and April 2022 were included. Pretransplant mycophenolate mofetil was started in November 2020. A comparison between patients who experienced intrahepatic cholangiopathy and who did not among ABO-incompatible transplantation was performed. Recipients of ABO-incompatible transplantations were categorized based on donor surgery into open, laparoscopy without pretransplant mycophenolate mofetil, and laparoscopy with pretransplant mycophenolate mofetil groups. Cox analysis of intrahepatic cholangiopathy was performed. A total of 234 ABO-incompatible transplantations were included. Intrahepatic cholangiopathy occurred in 1.1% (n=1/94), 13.3% (n=12/90), and 2.0% (n=1/50) of patients who received an ABO-incompatible liver with open surgery, laparoscopic donor surgery without pretransplant mycophenolate mofetil and laparoscopic donor surgery with pretransplant mycophenolate mofetil. ( p = 0.001) Multivariable analysis showed that transplantations involving a donor who underwent a laparoscopic hepatectomy and a recipient who did not receive pretransplant mycophenolate mofetil were associated with a higher risk of intrahepatic cholangiopathy (HR=13.449, CI=1.710-105.800, p = 0.02) compared with transplantations from donors who underwent open surgery. Transplantations involving a donor who underwent laparoscopic donor surgery and a recipient who received pretransplant mycophenolate mofetil resulted in no increased risk compared with transplantations from donors who underwent open surgery. (HR=5.307, CI=0.315-89.366, p = 0.25) Laparoscopic donor hepatectomy was a risk factor for intrahepatic cholangiopathy in ABO-incompatible liver transplantation, while pretransplant mycophenolate mofetil was related to risk reduction of intrahepatic cholangiopathy.