Background/Aims: Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus(R), a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus(R) system. Methods: Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus(R) on 2 consecutive days for >4 h. Results: Prometheus(R) treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus(R) treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. Conclusions: Prometheus(R) is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus(R) system are necessary to evaluate hard clinical end-points. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.