BackgroundOver 30 % of older patients experience hospitalization-associated disability (HAD) (i.e., loss of independence in Activities of Daily Living (ADLs)) after an acute hospitalization. Despite its high prevalence, the mechanisms that underlie HAD remain elusive. This paper describes the protocol for the Hospital-Associated Disability and impact on daily Life (Hospital-ADL) study, which aims to unravel the potential mechanisms behind HAD from admission to three months post-discharge.Methods/designThe Hospital-ADL study is a multicenter, observational, prospective cohort study aiming to recruit 400 patients aged ≥70 years that are acutely hospitalized at departments of Internal Medicine, Cardiology or Geriatrics, involving six hospitals in the Netherlands. Eligible are patients hospitalized for at least 48 h, without major cognitive impairment (Mini Mental State Examination score ≥15), who have a life expectancy of more than three months, and without disablement in all six ADLs. The study will assess possible cognitive, behavioral, psychosocial, physical, and biological factors of HAD. Data will be collected through: 1] medical and demographical data; 2] personal interviews, which includes assessment of cognitive impairment, behavioral and psychosocial functioning, physical functioning, and health care utilization; 3] physical performance tests, which includes gait speed, hand grip strength, balance, bioelectrical impedance analysis (BIA), and an activity tracker (Fitbit Flex), and; 4] analyses of blood samples to assess inflammatory and metabolic markers. The primary endpoint is additional disabilities in ADLs three months post-hospital discharge compared to ADL function two weeks prior to hospital admission. Secondary outcomes are health care utilization, health-related quality of life (HRQoL), physical performance tests, and mortality. There will be at least five data collection points; within 48 h after admission (H1), at discharge (H3), and at one (P1; home visit), two (P2; by telephone) and three months (P3; home visit) post-discharge. If the patient is admitted for more than five days, additional measurements will be planned during hospitalization on Monday, Wednesday, and Friday (H2).DiscussionThe Hospital-ADL study will provide information on cognitive, behavioral, psychosocial, physical, and biological factors associated with HAD and will be collected during and following hospitalization. These data may inform new interventions to prevent or restore hospitalization-associated disability.