Objective: To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients. Design: Prospective, randomized controlled pilot study. Setting: Single centre; interdisciplinary intensive care unit at a university hospital. Patients: Seventeen patients receiving CRRT. Interventions: Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180–210 s. Hirudin group (eight patients): continuous infusion of 10 µg/kg/h hirudin, dose was adjusted in 2 µg/kg/h steps with a targeted ecarin clotting time (ECT) of 80–100 s. Observation time was 96 h. Measurements and main results: Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P Conclusions: Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.