Citrate anticoagulation has not yet been described for hemodiafiltration (HDF) with high cut-off (HCO) membranes, which can be used in the treatment of cast nephropathy secondary to multiple myeloma. A 57-year-old male patient with multiple myeloma and acute renal failure was treated with HDF using a HCO membrane (Theralite) each or every other day. Due to thrombocytopenia, citrate anticoagulation was done for the first 7 h, and anticoagulant-free HDF was performed for the last hour to avoid citrate accumulation. Magnesium, phosphate, and albumin were measured after 3, 6, and 8 h, and were replaced as necessary. Thirty-two post-dilution HDF procedures (8 h each, infusate 24 L) were performed with blood flow at 300-330 mL/h; sodium citrate 4% was infused at 300 mL/h and 1 mol/L calcium chloride was infused at a mean rate of 14.6 ± 1.1 mL/h. Calcium-free dialysate/infusate was used. Ionized calcium was stable (1.10 ± 0.06 before and 1.08 ± 0.06 mmol/L after HDF). Magnesium was stable (0.67 ± 0.12 before and 0.68 ± 0.05 mmol/L after HDF), with an average 390 ± 180 mg per procedure, substituted orally. There was no metabolic alkalosis or hypernatremia after the procedures, and no significant clotting was noted. The total/ionized calcium ratio (1.87 ± 0.22 before vs. 1.56 ± 0.20 after 6 h) and the corrected/ionized calcium ratio (2.02 ± 0.21 before vs. 1.88 ± 0.27 after 6 h) decreased during HDF, indicating no citrate accumulation. Citrate anticoagulation was effectively performed during 8 h of HCO membrane HDF. There were no side effects of citrate anticoagulation, nor were any signs of citrate accumulation noted.