Most dialysis centers adopt a standard dialysate sodium prescription. While pre-hemodialysis (HD) serum sodium levels remain relatively constant in each individual patient on chronic HD, these levels can vary between different patients. Therefore, a single dialysate sodium prescription may not be appropriate for all patients. Nineteen stable patients on maintenance HD were dialyzed for 9 HD sessions with their current dialysis solutions, followed by another 9 sessions using individualized prescriptions created by aligning dialysate sodium levels to each patient’s serum sodium concentration. Patients were divided into 2 groups according to whether the average pre-HD serum sodium concentration was higher than (higher serum sodium group, n = 13) or equal to (equal sodium group, n = 5) the standard dialysate sodium concentration. Pre-HD serum sodium levels remained constant during entire study period in both groups. In higher serum sodium group, interdialytic weight gain increased after implementation of the sodium alignment (2.0 ± 0.3 kg vs. 2.3 ± 0.4 kg; P = 0.008). Thirst scores also increased in patients whose dialysate sodium was increased by 4 mmol/L (n = 7) (6.4 ± 1.5 vs. 7.6 ± 1.5, P = 0.015). There were no significant changes in blood pressure and intradialytic complications. In equal sodium group, significant differences were not observed in any parameters. Our results suggest that alignment of dialysate sodium levels to each patient’s serum sodium concentration is of little benefit in hemodynamically stable patients who have pre-HD serum sodium concentrations higher than dialysate sodium concentration.