In patients undergoing hemodialysis (HD) cyclic body fluid changes are estimated by body weight variations, which may be misleading. Conventional bioelectrical impedance analysis (BIA) produces biased estimates of fluids in HD due to the assumption of constant tissue hydration. We used an assumption-free assessment of hydration based on direct measurements of the impedance vector. The impedance vector (standard BIA at 50 kHz frequency) was measured in 1367 HD patients, ages 16 to 89 years with BMI 17 to 31 kg/m2, 1116 asymptomatic (680 M and 436 F), and 251 with recurrent HD hypotension (118 M and 133 F) before and after two HD sessions (thrice weekly bicarbonate dialysis, 210 to 240 min) removing 2.7 kg fluid. The vector distribution of HD patients was compared to 726 healthy subjects with the same age and BMI range. Individual vector measurements (resistance and reactance components) were plotted on the gender specific 50th, 75th and 95th percentiles of the vector distribution in the healthy population (reference tolerance ellipses) as a resistance-reactance graph (RXc graph). The wet-dry weight cycling of HD patients was represented on the resistance-reactance plane with a definite, cyclical, backward-forward displacement of the impedance vector. The vectors of patients with HD hypotension were less steep and more often shifted to the right, out of the reference 75% tolerance ellipse, than asymptomatic patients. A wet-dry weight prescription, based on BIA indications, would bring the vectors of patients back into the 75% reference ellipse, where tissue electrical conductivity is restored. Whether HD patients with vector cycling within the normal third quartile ellipse have better outcome awaits confirmation by longitudinal evaluation.