The incidence of systemic bleeding events and extracorporeal clotting was studied in 57 critically ill acute renal failure patients treated with intermittent hemodialysis (IHD) and/or continuous arteriovenous hemodialysis (CAVHD), using heparin (Hep), saline-flush (Sal, no anticoagulant), and citrate (Cit) anticoagulation protocols. Thirty-seven patients received a single dialysis modality, and 20 changed modalities one or more times, each change of dialysis type (IHD or CAVHD) or anticoagulant protocol being considered as a new course of treatment. The study was non-randomized, with a demonstrable bias towards using Hep for patients at lower risk of bleeding, and Sal or Cit for higher risk patients. Despite this bias, new bleeding events occurred during 26% of 35 courses of HepIHD and HepCAVHD, and during 0% of 24 courses of CitIHD and CitCAVHD (P < 0.009). Troublesome dialyzer/filter clotting occurred during one course of HepCAVHD, and during 12% of 129 SalIHD procedures; 28% of 29 courses of SalIHD were terminated for this reason. CitCAVHD was well tolerated and proved superior to other modalities in freedom from bleeding events and clotting problems. Alternatives to heparin anticoagulation should be made available for high risk patients requiring acute extracorporeal therapy.