Recent studies have focused on the association between dialysate sodium (Na+) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice‐weekly in‐center hemodialysis with an individualized dialysate Na+ prescription. Individualized dialysate Na+ was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na+ prescription (140 mEq/L) by 2–3 mEq/L until reaching a Na+ gradient of −2 mEq/L (dialysate Na+ minus average plasma Na+ over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre‐hemodialysis (HD) plasma Na+ concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na+ concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre‐ or post‐HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 13%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na+ reduces IDWG% without significantly increasing the frequency of cramps or hypotension.