Purpose: Infliximab, a chimeric monoclonal antibody that binds the tumor necrosis factor α (TNFα), is used in the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Previous cases of significant secondary liver disease associated with infliximab treatment have been reported in patients with RA, CD, and psoriatic arthritis including one case with fulminant hepatic failure (FHF) needing orthotopic Liver transplantation. Methods: We report one additional case of FHF in a 25 yr Old man with RA who developed a FHF secondary to autoimmune hepatitis with infliximab treatment. Results: A 25-year old man with Juvenile Rheumatoid Arthritis and Still's disease who was on Infliximab (300 mg IV infusion once every three weeks) since the last three years was transferred from a different hospital to our center with jaundice, lethargy, poor appetite and rapidly worsening liver function tests. His aspartate aminotransferase (3,575 IU/mL), alanine aminotransferase (4,521 IU/mL), alkaline phosphatase (121 IU/mL), total bilirubin (16.6 mg/dl) and direct bilirubin (12.5 mg/dl) levels were significantly elevated at admission. Partial thromboplastin time (PTT 41.1) and prothrombin time (PT 40 sec) were also elevated with INR of 4.1 at admission and which continued to rise on follow-up. He had no history of hepatic diseases, exposure to hepatotoxic or illicit drugs, or alcohol abuse. Multiple laboratory tests were done for hepatitis A (IgM/IgG Anti-HAV), B (HBsAg, antiHBS, antiHbc, HBV DNA), C (anti-HCV and HCV PCR), E (IgG HEV), G (Hepatitis G RNA PCR) and cytomegalovirus (CMV DNA PCR), herpes simplex virus (IgG HSV-1), EBV caspid Ag (IgG Ab, IgM- Ab), EBV PCR, Varicella Zooster (IgG) and was notably all of which were negative. His Iron profiles were within normal limit (S. Iron 161, TIBC 171, Transferrin sat 94%). Alfa-1-antitrypsin was within normal range (171 mg/dl). His Ferritin levels were high likely reflecting the status of an acute phase reactant. AFP levels were mildly elevated (20.9 ng/Ml). Serum protein electrophoresis showed a polyclonal increase in the gamma region. He fulfilled autoimmune hepatitis type 1 criteria [ANA (1:320), ASMA (1:160) and Ds-DNA (+)] at admission. Despite aggressive treatment with oral prednisone he developed progressive hepatic failure. After the onset of hepatic encephalopathy on the 5th day of the hospital admission a liver transplant was performed successfully. Liver allograft was consistent with autoimmune hepatitis. Conclusion: This case should alert rheumatologists and the hepatologist to the possibility of serious adverse reactions associated with the use of TNFα blockers and the potential to cause autoimmune hepatitis leading even to fulminant hepatic failure.