Graft versus host disease (GVHD) occurs quite often after hematopoietic cell transplantation. However, it is a rare complication after solid organ transplantation and consists of a reaction of donor-derived immune cells directed against host tissues, which is mostly seen in liver, small intestine, and pancreas transplantation. We are presenting a 54-year-old man with a long-standing history of hypertension, hypertensive nephrosclerosis, and stage V terminal chronic kidney disease, who was on a regular hemodialysis thrice weekly. He had a living kidney transplantation done abroad. On returning, he had a normal kidney function with no obvious complications. Three years later, he presented with jaundice, anorexia, diarrhea, and abdominal pain. Laboratory evaluation showed marked elevated liver enzymes, and severe pancytopenia with evidence of hepatosplenomegaly. Liver biopsy was compatible with graft-versus-host-disease and toxic hepatitis. The patient was not cooperative with the management and he traveled abroad for the 2nd opinion. Based on the clinical presentations, laboratory, radiological, and pathological findings, transplant-associated GVHD (ta-GVHD) was confirmed. Unfortunately, this patient was complicated by severe sepsis, and confounded by a lack of cooperation with the management plan, which resulted in his demise. In the presence of a highly immunocompromised state, patients presenting with transaminitis/hyperbilirubinemia, and when drug-induced liver injury is excluded, the diagnosis of ta-GVHD needs to be highly considered.