The consequences of newer techniques of continuous renal replacement therapy in critically ill patients are not yet fully known. The clinical and biochemical impact of continuous veno-venous hemodiafiltration (CVVHD) was, therefore, prospectively studied in 60 critically ill patients with acute renal failure. Prospective clinical, biochemical, and hematological data were collected from patients receiving CVVHD. Over the initial 24 hours of therapy, CVVHD resulted in a decrease in mean plasma urea from 34.5 mmol/L (95% confidence interval [CI], 29.4 to 39.6) to 25 mmol/L (95% CI, 21.8 to 28.2). With continued CVVHD, the mean plasma urea reached a plateau level of 17.6 mmol/L (95% CI, 15.8 to 19.4) at 72 hours. This degree of azotemia control was achieved with ease and essentially without complications during 8,360 hours of therapy despite the presence of multi-organ failure and the aggressive administration of protein nitrogen (0.25 to 0.35 g/kg/day). No abnormalities of serum electrolytes developed during treatment. Survival to intensive care discharge was 46.6% and to hospital discharge 41.6%, despite a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score at presentation of 27.7. Continuous veno-venous hemodiafiltration offers superior azotemia control and a safe approach to renal replacement therapy in critically ill patients. Its use is associated with a comparatively favorable outcome. CVVHD may be regarded as the treatment of choice in such patients.