Introduction We aimed to investigate the effect of a standard hemodialysis prescription in hyponatremic patients requiring hemodialysis on the development of osmotic demyelination syndrome. Methods Ninety-nine patients who were treated with hemodialysis for the first time and had a pre-dialysis sodium value of <= 125 meq/L included in the study. Standard hemodialysis treatment was applied to all patients. Biochemical data before, immediately after and 24 h after hemodialysis were recorded retrospectively. All patients followed up for 2 weeks and magnetic resonance imaging was performed in patients with neurological symptoms. Results Eight patients had a sodium increase of more than 12 meq/L at 24-h after hemodialysis. Although hyponatremia was corrected rapidly with hemodialysis, none of the 99 azotemic patients developed osmotic demyelination syndrome. Conclusion We did not observe osmotic demyelination syndrome in hyponatremic patients with azotemia treated with standard protocol hemodialysis. However, caution should still be exercised in high-risk patients for osmotic demyelination.