Introduction Falls are the most common type of safety incident reported by acute hospitals and can cause both physical (eg, hip fractures) and non-physical harm (eg, reduced confidence) to patients. It is recommended that, in order to prevent falls in hospital, patients should receive a multifactorial falls risk assessment and be provided with a multifactorial intervention, tailored to address the patient’s identified individual risk factors. It is estimated that such an approach could reduce the incidence of inpatient falls by 25%–30% and reduce the annual cost of falls by up to 25%. However, there is substantial unexplained variation between hospitals in the number and type of assessments undertaken and interventions implemented. Methods and analysis A realist review will be undertaken to construct and test programme theories regarding (1) what supports and constrains the implementation of multifactorial falls risk assessment and tailored multifactorial falls prevention interventions in acute hospitals; and (2) how, why, in what contexts and for whom tailored multifactorial falls prevention interventions lead to a reduction in patients’ falls risk. We will first identify stakeholders’ theories concerning these two topics, searching Medline (1946–present) and Medline In-Process & Other Non-Indexed Citations, Health Management Information Consortium (1983–present) and CINAHL (1981–present). We will then test these theories systematically, using primary studies to determine whether empirical evidence supports, refutes or suggests a revision or addition to the identified theories. Ethics and dissemination The study does not require ethical approval. The review will provide evidence for how to implement multifactorial falls risk assessment and prevention strategies in acute hospital settings. This will be disseminated to academic and clinical audiences and will provide the basis for a future multi-site study through which the theories will be further refined. Systematic review registration PROSPERO CRD42020184458.