Major resection of cirrhotic livers can result in hepatic failure, but no supportive treatment has been found to be generally effective. We successfully treated a 63-year-old woman with post-hepatectomy liver failure with plasmapheresis. Following right hepatectomy, the initial postoperative recovery of liver function was favorable, except for ascites. One month later, however, the amount of drained ascites increased up to 2 l/day. In addition, serum cholesterol concentration gradually decreased to around 30 mg/dl, and serum total bilirubin rose to 11.1 mg/dl. Plasmapheresis was performed, and after just 2 sessions, serum cholesterol level was rapidly corrected and prothrombin time was restored. After 3 sessions of plasmapheresis, the usual rebound rise of serum bilirubin disappeared, and the amount of ascites drained also decreased slowly. The patient underwent a total of 5 sessions of plasmapheresis over 2 weeks, after which liver function improved slowly, and she was finally discharged 72 days after liver resection. Mild ascites requiring diuretic therapy persisted over 3 months. She is doing well to date 10 months after liver resection without tumor recurrence or hepatic decompensation. This limited experience suggests that plasmapheresis can be a useful liver support for post-hepatectomy liver failure.