Background/Aims: Continuous venovenous hemofiltration (CVVH) requires anticoagulation to prevent circuit clotting and its use is contraindicated in patients with high bleeding risk. The aim of this study was to compare CVVH with and without regional citrate anticoagulation (RCA) with respect to filter life, azotemic control and cost. Methods: This was a prospective sequential cohort study. The first cohort of patients with a high bleeding risk and acute renal failure was treated by anticoagulant-free predilution CVVH (n = 31). In the second cohort, CVVH was applied with RCA (n = 20). Results: The median filter life was 41 h (interquartile range 20–62) with RCA and 12 h (8–28) without RCA (p = 0.001). The azotemic control was better in the group with RCA. The hourly cost was comparable between the two groups. Conclusion: Regional anticoagulation with citrate-based replacement solution improved filter life compared to anticoagulant-free predilution CVVH. This regimen appeared safe, feasible and without metabolic complications or increased costs.