The introduction of High Flux (HF) haemodialysers and their application in single dialyser haemodiafiltration (sdHDF) for patients on extracorporeal dialysis (ECD) therapy has improved the extraction of uraemic toxins, including the low molecular weight protein (LMWP) beta 2 microglobulin (β2M, 11.6kDa). Similar increases in the extraction of protein-bound uraemic toxins (PBUT) and larger LMWP (15-50kDa) remain elusive. High concomitant losses of albumin prohibit the use of Medium Cut-Off (MCO) or protein-losing haemodialysers for sdHDF to increase the extraction of these molecules by convective transfer. A new extracorporeal dialysis treatment modality, dual dialyser haemodiafiltration (ddHDF), has been designed together with a mathematical model to compare its predicted performance to that of sdHDF in the extraction of solute. The extra process that distinguishes ddHDF from sdHDF is the secondary ultrafiltration and partial re-infusion of the effluent haemodiafiltrate from the primary haemodialyser. This allows MCO and protein-losing haemodialysers to be used to increase the extraction of both LMWP and PBUT without excessive concomitant loss of albumin. Data from the mathematical model show that ddHDF could increase the extraction of smaller and larger LMWP by an extra 102% and 220% respectively compared to standard HF sdHDF, whilst restricting the loss of albumin to 0.83 grams per hour of treatment. In using albumin as a recyclable carrier molecule for the extraction of PBUT from plasma ddHDF has the potential to increase PBUT reduction ratios (RR's) to 49% by convection alone. Even higher RR's are possible if the dialysate volume flow rate can be increased beyond 600ml/min. ddHDF provides an opportunity for a step change increase in the level of extraction of both larger LMWP and PBUT in patients with end stage kidney disease.