Acute graft-versus-host disease (GVHD) following orthotopic liver transplantation is a rare but severe disease with a 75% death rate in adults. Various therapeutic strategies have been proposed for steroid-refractory GVHD, but there is still no consensus. Tumor necrosis factor-alpha is a key inflammatory cytokine involved in acute GVHD physiopathology, and infliximab has shown encouraging results for the treatment of acute GVHD following hematopoietic stem cell transplantation. We report the first case of acute GVHD following liver transplantation that was refractory to steroids and anti-lymphocyte globulin but was successfully treated with infliximab.