Nimesulide is a non-steroidal anti-inflammatory drug available in several European countries. A hepatic toxicity due to nimesulide has been reported but fatal cases remain rare. We report the case of a 49-year-old woman treated by nimesulide during three days, admitted to the intensive care unit for an acute liver failure with encephalopathy. A temporary hepatic support by molecular adsorbent recirculating system (MARS) was performed and a hepatic transplantation was performed 12 hours after admission, allowing a rapid improvement and a discharge from intensive care unit four days after transplantation. Nimesulide induced hepatic toxicity is unpredictable and the intensity of symptomatology is variable. Clinical symptoms are often progressive, delayed from the onset of treatment. Our case draws attention to the risk of hepatic failure related to treatment with nimesulide, leading to hepatic transplantation or death. The question of risk/benefit ratio must be asked again for this widely used molecule.