<b><i>Background:</i></b> Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. <b><i>Method:</i></b> ­Albumin removal was compared in vitro between 3 pre-­dilution-HCO-CVVHDF with citrate anticoagulation and 3 ­HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. <b><i>Results:</i></b> Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. <b><i>Conclusion:</i></b> HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher ­albumin transmembrane removal compared to HCO-CVVHD.