Due to the crucial role of hypovolemia in the genesis of dialysis-induced hypotension, we have evaluated whether the automatic control of the intradialytic blood volume (BV) decrease along a preset trajectory might be beneficial to the hemodynamic stability during treatment. Five frequently hypotensive HD patients were studied and a 3-period-protocol (A1-B-A2) was adopted, each period lasting 6 sessions per patient. During the B periods the patient BV decrease was kept along a predefined profile, thanks to an automatic system with a retroactive control of both the ultrafiltration rate (UFR) and dialysate conductivity (DC); instead, during the A periods, conventional HD was performed, with linear UFR and constant DC, inducing a spontaneous decrease in BV. The intradialytic BV behaviour was much more stable during the B-periods (-10.2 ∓ 1.4% by the end of the treatment) than during the A1 (-11.2 ∓ 3%) and A2 periods (-11.5 ∓ 2.5%). Only one dialysis-hypotension episode was observed during the B periods, compared to 8 and 5 during the A1 and A2 periods, respectively (p ≤ 0.05). The automatic control of the BV changes during dialysis could improve the intra-treatment cardiovascular stability in critically-ill patients.