Introduction: Little is known about the role of the organisational culture in the success and sustainability of the hospital-wide interventions, and how local culture affects patient outcomes in acute hospitals. Methods and analysis: A systematic literature review will be conducted to identify organisational factors influencing hospital-wide interventions and patient outcomes. A search of English language articles will be performed in MEDLINE, CINAHL, EMBASE, Web of Science, PsychInfo and Global Health databases using Medical Subject Headings and keywords. Randomised controlled trials, quasi-randomised trials, controlled before and after design studies and interrupted timeseries analysis studies will be included. 'Grey literature' will be excluded, however peer-reviewed journals that are likely to publish relevant studies (JAMA, BMJ, BMJ Quality and Safety, Lancet and New England Journal of Medicine and Implementation Science) will be hand searched for the last 5 years. Two reviewers will independently undertake a title and abstract review using inclusion and exclusion criteria. Studies will be excluded only after discussion between at least two reviewers, who will assess and agree on the inclusion, risk of bias and quality rating of the studies. One author will extract summary descriptive data from these studies; the other author will review this documentation for accuracy and completeness. Results: It is likely that the studies will be heterogeneous in nature, therefore a narrative synthesis of the findings will be conducted. Conclusions: We will discuss characteristics of the studies and stratify the results according to the type of hospital-wide interventions, organisational factors associated with them and outcomes measured.