Abstract Background and Aims The dialysate sodium prescription remain unclear as an important component of sodium balance in HD patients Pre-hemodialysis (pre-HD) serum sodium levels can vary among different patients, therefore, a single dialysate sodium prescription may not be appropriate for all patients. Dialysate sodium is one of the most easy changeable parameter which can influence hemodynamic stability. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of prescription of different models of dialysate sodium Method 77 nondiabetic subjects (41 men; 36 women) performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration set up at 138 mmol/L, followed by additional 3 models of dialysate sodium (each model performed 2 months sessions with 2 months standard dialysate sodium between each model) wherein dialysate sodium was set up: model 1: according to pre-HD serum sodium concentration, model 2: according to sodium concentration in UF fluid, model 3: sodium profiling ( from 144 to 136 mmol/L). Blood pressure (BP), interdialytic weight gain (IDWG), thirst score, sodium gradient were analysed. After the standard dialysate sodium hemodialyses, the subjects were divided into 3 groups: normotensive (N=58), hypertensive (N= 14) and hypotensive (N=5) based on the average pre-HD systolic BP during the standard dialysate sodium hemodialyses. Results Model 1: resulted in significantly lower blood pressure (133,61±11.88 versus 153.60±14.26 mmHg; p=0.000) and IDWG (2.21±0.93 versus 1.87±0.92 kg; p=0.018) in hypertensive patients, whereas normotensive patients showed only significant decrease in IDWG (2.21±0.72 versus 2.06±0.65, p=0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p<0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. Thirst score was significantly lower in all patients with individualized-sodium HD and the use of antihypertensive drugs significantly reduced in hypertensive patients during the individualized phase. Model 2: resulted in significantly lower BP in normotensive and hypertensive patients (126.92±9.71 versus 124.08±8.71 mmHg; p=0.000; 153.60±14.26 versus 138.91±8.48 mmHg, accordingly), with no influence on IDWG, thirst score compared to standard dialysate sodium. Model 3: significantly higher BP and IDWG in all 3 groups (normotensive 126.92±9.71 versus 130.20±9.5 mmHg; p=0.001; IDWG 2.21±0.72 versus 2.34±0.82 kg, p=0,005; hypertensive 153.60±14.26 versus 157.58±5.0 mmHg; IDWG 2.21±0.93 versus 2.39±0.74 kg; p=0.005; hipotensive 79.81±11.78 versus 91.09±24.98 mmHg, IDWG 2.53±0.57 versus 2.73±0.15 kg, p=0.005) and significantly higher thirst score in normotensive and hypotensive patients, with no influence in hypertensive patients. Conclusion A reduction of the dialysate sodium concentration based on the pre HD serum sodium level of the patient, reduced the BP, IDWG, thirst score and use of antihypertensive drug compare to dialysate sodium according to sodium concentration in UF or sodium profiling. We recommend prescription of dialysate sodium according to pre HD serum sodium concentration.