We expect heterogeneity and to conduct a qualitative synthesis of the results. We will assess risk of bias in included studies using the Quality in Prognosis Studies tool for prognostic studies and the Newcastle-Ottawa Scale for observational studies. From included studies, bibliographical and study description data, patient characteristics, and data related to prevalence of organ failure and prognosis will be extracted. Included studies will have assessed the prevalence or prognosis, defined as mortality or ICU transfer, of new onset organ failure. Eligible studies will include an unselected group of acutely ill adult patients at arrival to hospital, with one or more organ failures (respiratory, renal, cerebral, circulatory, hepatic, or coagulation failure). By an independent full-text screening, two authors will decide on the eligibility for the remaining studies. One author will perform the title and abstract screening and exclude obviously ineligible studies. The information sources used are electronic databases, PubMed, Cochrane Library, EMBASE, and CINAHL references in included studies and review articles and authors’ personal files. The result of the review will assist physicians working in an ED, when assessing patients’ risk of organ failure and their associated prognosis. This systematic review aims to identify, summarize, and analyze studies of prevalence and prognosis of new onset organ failure in acutely ill undifferentiated patients, at arrival to hospital. The prevalence and prognosis of acutely ill patients, with organ failure, at arrival have been studied in some selected groups, but methods and results differ. Before patients arrive to the intensive care unit, or the general ward, most of them have passed through the emergency department (ED), where diagnosis and treatment has been initiated. Most studies on organ failure have been performed in intensive care settings, or on selected groups of patients, where a high prevalence and mortality have been reported. As the prognosis of organ failure improves with early treatment, it is important to identify these patients as early as possible. Acutely ill patients are a heterogeneous group, and some of these suffer from organ failure.