Adult living donor liver transplantation (LDLT) was developed against the background of a scarcity of deceased donors and has a number of disadvantages leading to in-hospital mortality, such as marginal donors and grafts and recipients suffering from severe conditions. We have thus developed surgical and medical innovations to overcome these disadvantages. The present study analyzes the causes of death and factors affecting in-hospital mortality in adult recipients of LDLT. Between November 1994 and December 2007, 576 consecutive adult patients underwent LDLT at a single medical center. Overall in-hospital mortality was 18.9%. The peak rate was 55.6% in 1996, and the rate gradually decreased thereafter to 4.4% in 2007. The most frequent cause of death was infection (62.5%), which was followed by rejection (15.7%) and nonseptic multiple-organ failure (8.9%). Being intensive care unit-bound before the operation, ABO blood type incompatibility, an absence of postoperative enteral nutrition, and a Model for End-Stage Liver Disease score of 25 or higher were independent risk factors for in-hospital mortality. In ABO-identical and ABO-compatible cases, retransplantation and a positive lymphocyte crossmatch test were additional independent risk factors. In conclusion, even aggressive efforts, preoperative conditions such as being intensive care unit-bound, a high Model for End-Stage Liver Disease score, retransplantation, and a positive lymphocyte crossmatch test are still risk factors. Enteral nutrition could be a promising strategy to improve adult LDLT.