Introduction: The prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes. Methods and analysis: A prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy ( July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months. Ethics and dissemination: This protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento ( protocol numbers 61-62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F ( protocol number 0041708; 23/7/2013), USL Latina ( protocol number 20090/A001/ 2011; 12/7/2013), Trapani ( protocol number 3413; 16/ 7/2013) and Brindisi ( protocol number 40259; 6/6/ 2013). All participants have provided written and informed consent and can withdraw from the study at any time. The findings of the study will be disseminated through peer-reviewed journals and national and international conference presentations and to the participants through communication within the dialysis network in which this study is conducted.