BACKGROUND: Cognitive impairment (CI) and dementia are common in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Their cause is multifactorial. Our study is first to compare the impact of hemodialysis (HD) and online hemodiafiltration (HDF) on patients' cognitive outcomes. METHODS: This was a cross sectional, multicenter cohort study. Adult ESRD patients aged >18 years on regular high flux HD or online HDF were recruited in the study. Clinical, laboratory, daily activities and cognitive functions assessment were assessed in all the involved individuals. RESULTS: A total of 241 patients were successfully recruited into the study: 164 treated with high flux HD and 77 treated with HDF. Hypertension and diabetes were the commonest associated comorbidities. 85.9% of patients were functionally independent with no significant difference between those on HD versus HDF. 81.3% of our patients showed different degrees of CI. HDF has no superiority in the improvement of cognitive functions. Age, vitamin D level and haemoglobin (Hb) were the most independent predictors of cognitive function impairment among HD patients. CONCLUSIONS: Cognitive function impairment is a common problem in hemodialysis and is associated with multiple risk factors. HDF showed no beneficial effect over HD. There is no superiority of online HDF versus high flux HD in improving cognitive functions.