Several extracorporeal techniques have been used to remove N-acetylprocainamide (NAPA), the major metabolite of procainamide, in patients intoxicated with this substance. We report a patient with life-threatening NAPA intoxication who was rapidly and successfully treated with combined high-efficiency hemodialysis and charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed in series such that the patient’s blood was dialyzed before reaching the cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88 mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal circuit resulted in a 50% increase in clearance over that obtainable by high-efficiency hemodialysis alone. In comparison to other modalities, this technique is more effective than either hemodialysis or charcoal hemoperfusion alone and can achieve a more rapid reduction of serum NAPA levels than that observed with slow continuous hemofiltration or hemodiafiltration.