Regional citrate anticoagulation (RCA) is not widely used because it requires complex therapeutic modalities, a specialized calcium-free replacement solution, and continuous intravenous calcium infusion. We designed a simplified protocol for RCA using a commercial calcium-containing replacement solution for continuous venovenous hemofiltration (CVVH). Thirty-six patients were treated with RCA-based pre-dilution CVVH using a calcium-containing replacement solution (ionized calcium 1.50 mmol/L). We pumped a 4 % trisodium citrate solution into the arterial line of extracorporeal circulation at a starting rate of 200 mL/h while adjusting the rate to achieve a post-filter ionized calcium level of between 0.25 and 0.5 mmol/L. The initial blood flow was set at 150 mL/min. The replacement solution was delivered at 35 mL/kg/h. We measured the serum and effluent citrate concentration during CVVH at 0, 24, 48, and 72 h. The mean hemofilter survival was 61.3 ± 21.6 h (range 14-122 h). The mean 4 % trisodium citrate solution pumped was 207 (190-230) mL/h, and the mean pre-filter and post-filter ionized calcium levels were 0.96-1.02 and 0.34-0.38 mmol/L, respectively. Ninety-two, 63, and 48 % of the hemofilters were patent at 24, 48, and 72 h. The mean serum citrate concentration was not significantly different at 24, 48, and 72 h. No bleeding episodes were found, and no patient showed the symptoms and signs of hypocalcemia or citrate toxicity. Our simplified RCA protocol using a calcium-containing replacement solution for CVVH is effective and safe, and obviates the need for a separate peripheral or central venous catheter for continuous intravenous calcium infusion.