We examined whether progressive reduction of dialysate sodium with Diacontrol (DC, plasma conductivity targeted feedback system) confers any clinical benefit over a similar strategy using dialysis with fixed dialysate conductivity (HD). Ten stable patients entered a randomized crossover study conducted over 360 dialysis sessions. Sodium balance, blood pressure (BP), intradialytic hypotension rates (IDH), thirst score, and extracellular water (ECW) were recorded. Interdialytic ambulatory BP was measured at the highest and lowest conductivities. BP, interdialytic weight gains and thirst scores were low at the outset and were not altered significantly by conductivity reduction. The lowest fixed dialysate setting of 13.2 mS/cm resulted in greater sodium depuration than the lowest conductivity setting allowable with DC, as reflected by lower post dialysis plasma conductivity (13.4 ± 0.14 mS/cm versus 13.5 ± 0.04 mS/cm, p < 0.001). Predialysis ECW fell from 0.22 ± 0.04 l/kg to 0.21 ± 0.09 l/kg as conductivity reduced with HD (p < 0.05), but did not change significantly with DC. When HD and DC were matched for end-dialysis plasma conductivity, there were no differences in BP, IDH frequency, or dialysis tolerability even at the lowest conductivity settings. In a setting of dialysate sodium reduction, DC did not appear to have any short-term clinical advantage over standard dialysis, and its range is limited at the lower conductivity settings.