Background: Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF.Objective: To investigate efficacy and safety of RRT in horses. Animals: Five healthy adult horses. Methods: A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period.Results: Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P .007). A significant increase in serum phosphorus (P .001) and decrease in BUN (P < .001) were also noted. A significant prolongation of prothrombin (P < .01) and partial thromboplastin time (P < .0001) were observed along with a decrease in platelet count (P .04). Conclusions and Clinical Importance: Renal replacement therapy can safely and effectively be used in adult horses.