Background: Handwriting is a skill that needs the integration of musculoskeletal and nervous actions. It could be affected by debilitating diseases like an end-stage renal disease. Hemodialysis patients are at increased risk for cognitive impairment, psychological deficiencies, and metabolic changes which can influence the quality of handwriting. Aim of work: To investigate the effect of hemodialysis in a sample of end-stage renal disease patients on their handwriting. Patients and methods: This study included 110 end-stage renal disease patients on hemodialysis. They wrote two samples, one before and one after hemodialysis sessions with the unification of writing materials. Their handwriting was examined for word size, word spacing, pressure of writing, slanting direction of words, types of strokes, and overwriting. Results: among the studied patients, males were 61.8% and females were 38.2%. Most patients (70%) were on regular hemodialysis for less than 10 years. After hemodialysis 40.9% of the patients had increased word size, 14.5% had increased word spacing, 10.9% had weaker pressure of writing than before hemodialysis, and 44% showed strokes and overwriting. Extra strokes were the most common type that appeared after hemodialysis (25.5%). There were no significant associations between the presence of other concomitant diseases or the duration of hemodialysis and all the studied individual handwriting characteristics. Whereas increased word size and overwriting after hemodialysis were significantly higher in patients with medium-level education in comparison to other education levels. Conclusion: Hemodialysis therapy could affect patients' handwriting characteristics to a certain degree regardless of the duration of end-stage renal disease.