Continuous renal replacement therapy (CRRT) is widely used in the management of septic patients with acute renal failure (ARF). Short filter lifespan (<24 hours) is a major concern and may result of a procoagulating state. The aim of this study was to investigate the relationship between antithrombin (AT) deficit and early filter clotting, and whether supplementation of AT could increase filter lifespan. Two different methods for supplementation, bolus and continuous infusion were also compared. We conducted a two-center prospective study from March 2003 to May 2004. Twenty-seven patients with septic shock and ARF were included and treated by CRRT. Unfractionated heparin (UHF) was used for anticoagulation. The initial level of AT was low with a median level at 45.4% (16%-69%). Low AT activity was associated with shorter filter lifespan. Supplementation led to a longer filter lifespan (15.2-33.2 hours) (p < 0.05). Continuous infusion provided better results: 48.5 vs. 27.8 hours for bolus method. This study suggests that AT measurement should be considered in continuous veno-venous hemofiltration with clotting problems as supplementation could increase filter lifespan by more than 100%. Continuous infusion is preferable. Cost effectiveness should be evaluated shortly.