Background/Aims: To evaluate the efficacy and safety of regional citrate anticoagulation (RCA) plus low-dose dalteparin in patients receiving continuous veno-venous hemofiltration (CVVH). Methods: Patients requiring pre-dilution CVVH at 4 l/h were randomly assigned to group A (RCA only), group B (normal-dose dalteparin anticoagulation only) or group C (RCA plus low-dose dalteparin). The primary endpoint was filter runtime and the secondary endpoints were premature clotting of the filter and anticoagulation-related side effects. Results: Fifty-three patients completed the study. The mean filter runtime was significantly longer in group C (40.4 ± 30.9 h) than those in group A (21.2 ± 13.5 h, p = 0.006) and group B (25.1 ± 24.0 h, p = 0.040). The rate of premature clotting, new onset of bleeding, hypocalcemia and metabolic acidosis did not differ significantly in three groups. Conclusions: RCA plus low-dose dalteparin prolonged filter runtime compared with RCA only or normal-dose dalteparin only without increasing the incidence of anticoagulation-related complications.