Objectives: To compare filter survival times during high-volume, continuous venovenous hemofiltration in patients with normal coagulation variables, using anti-factor Xa bioequivalent doses of nadroparin and dalteparin. To evaluate which other factors influence filter survival time. Design: Randomized, prospective, double-blind, crossover study. Setting: An 18-bed intensive care unit in a 530-bed teaching hospital. Patients: Thirty- two critically ill patients with renal failure, treated with high-volume, continuous venovenous hemofiltration. Interventions: High-volume, postdilutional continuous venovenous hemofiltration, with a standard blood flow rate of 200 mL/min and an ultrafiltrate volume of 100 L in 24 hrs, was performed with a highly permeable, large-surface cellulose triacetate membrane. Anticoagulation with anti-Xa bioequivalent doses of nadroparin and dalteparin was administered in the extracorporeal line before the filter. Blood was sampled for determination of coagulation variables before hemofiltration, 0.5, 2, 4, 6, and 12 hrs after starting the treatment, and at the end of the hemofiltration run. Measurements and Main Results: Anti-Xa peak activity, time of anti-Xa peak activity, area under the curve for 0-3 hrs and filter survival time were not significantly different using nadroparin or dalteparin. When analyzing the patients according to the length of filter survival time, no relationship among anti-Xa peak activity, area under the curve for 0-3 hrs, and filter survival time was found. However, there was a strong trend toward a negative correlation between baseline platelet count and filter survival time (r2 = .11; p = .07). Mean blood urea nitrogen decreased from 81.0 ± 31.9 to 41.1 ± 21.2 mg/dL (p < .01) and mean creatinine decreased from 3.4 ± 1.8 to 1.9 ± 1.2 mg/dL (p < .01). There were no clinically important bleeding complications. Conclusions: Nadroparin and dalteparin are bioequivalent with respect to their anti-Xa activities. Using either drug, we did not find a difference in filter survival time during high-volume, continuous venovenous hemofiltration. No relationship between anti-Xa activity and filter survival time could be found. However, there is a strong trend toward a negative correlation between baseline platelet count and filter survival time. This suggests that during high- volume, continuous venovenous hemofiltration, patients with a higher baseline platelet count might need a different anticoagulation regimen to obtain longer filter survival times.