Regional citrate anticoagulation should be a simple process of substituting hypertonic (1.6 mol/L) citrate for heparin and adjusting the infusion to obtain an arterial activated clotting time of 150 to 200 seconds. Serious, documented complications of citrate anticoagulation involve citrate intoxication during isolated ultrafiltration; hyperaluminemia, hyperammonemia, and hypernatremia during sorbent dialysis; and profound alkalosis, paresthesias, arrhythmia, and cardiac arrest during bicarbonate dialysis. We suspected that some of these complications could be avoided by using anticoagulant citrate dextrose-A (ACD) rather than hypertonic tri-sodium citrate (TSC) as the anticoagulant. In a cross-over study with random assignment order eight adults underwent mid-week dialyses with ACD (0.113 mol/L citrate) and TSC (1.6 mol/L citrate) regional citrate anticoagulation. Predialysis to postdialysis changes in Na (mEq/L), Ca (mg/dL), ionized Ca (mg/dL), pH, and HCO3 (mEq/L) are listed below. [Table in journal] Using continuous blood flow and avoiding isolated ultrafiltration and sorbent dialysis should prevent the delivery system complications of regional citrate anticoagulation. During this evaluation isotonic and hypertonic citrate resulted in similar serum sodium changes, and standard dialysate effectively reversed the citrate/calcium interaction of both hypertonic and isotonic citrate infusions to restore homeostasis without a separate calcium infusion. The combination of TSC and bicarbonate dialysate does produce a profound metabolic alkalosis, which is lessened by using ACD. In general, regional citrate anticoagulation is simplified by using standard dialysate with a hypertonic rather than an isotonic citrate infusion, and dangerous complications are further evaded by adjusting the dialysate bicarbonate to 25 to 30 mmol/L or substituting a mixture of citric acid and TSC (ACD) for TSC.