Over the past several years, continuous venovenous hemodiafiltration (CVVHDF) using pump-driven devices has gained wide acceptance as a form of renal replacement therapy for critically ill patients with acute renal failure. More recently, regional citrate anticoagulation has proven useful as a method of anticoagulating CVVHDF circuits, particularly in those patients at high risk for bleeding. However, an easy and convenient method for guiding the dose of citrate infusion has not previously been described. We describe the use of an algorithm using posthemofilter levels of ionized calcium to guide the dose of administered regional citrate on the survival time and urea and creatinine clearances of 24 Hospal AN69HF hemofilters. Nine patients with acute and chronic renal failure requiring CVVHDF were studied. The median filter survival time when using the postfilter ionized calcium algorithm was 3.4 days, with a survival probability of 46% (95% confidence interval [CI], 17 to 71). Random-effects linear regression analysis did not show a significant decline in blood-side urea clearance (P = 0.041) or creatinine clearance (P = 0. 308). Moreover, definite bleeding complications occurred with an incidence rate of 0.045/person-day on citrate anticoagulation (95% CI, 0.006 to 0.16), and occult bleeding occurred with an incidence rate of 0.091/person-day on citrate anticoagulation (95% CI, 0.03 to 0.23). Guiding regional citrate anticoagulation through the use of posthemofilter ionized calcium levels is a safe and effective method of prolonging filter life during CVVHDF.