BACKGROUND: The prevalence of drug-drug interactions (DDIs) in hospital settings is variable, and elderly patients are considered a high risk population for DDIs. There are no systematic reviews describing the prevalence of DDIs in hospitalised elderly patients. OBJECTIVES: To assess and summarise the available data on the prevalence of DDIs in hospitalised elderly patients and to describe which drugs, drug classes and drug combinations are most commonly involved in DDIs. DATA SOURCE: A systematic electronic literature search was conducted on Medline/PubMed, Embase, Lilacs, SciElo, Web of Science, Cinahl, Scopus, Cochrane, OpenGrey, Capes Thesis Bank, OasisBR, OpenAire and abstracts from scientific events, without limitation on language or period of publication. Study selection was completed on 21 September 2018. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Original observational studies that reported the prevalence of actual or potential DDIs during hospitalisation in patients aged 60 years or older were included. The main outcome measure was prevalence of DDIs and number of DDIs per patient. Subgroup analysis was performed in studies that reported the prevalence of DDIs in geriatric units. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Agency for Healthcare Research and Quality methodological checklist for cross sectional and prevalence studies. RESULTS: 34 studies were included, involving 9577 patients. The prevalence of DDIs ranged from 8.34% to 100%. In studies conducted in geriatric units, the prevalence ranged from 80.5% to 90.5%. The number of DDIs per patient ranged from 1.2 to 30.6. Single drugs most commonly involved in DDIs were furosemide, captopril, warfarin and dipyrone. Drug classes mostly involved were potassium sparing diuretics and angiotensin converting enzyme inhibitors. LIMITATIONS: The main limitation is the heterogeneity between the included studies that precluded a meta-analysis. Several different methods were used to identify DDIs, majorly, and potential DDIs. Few studies have reported measures to control the quality of the collected data. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The prevalence of DDIs ranged widely, and the variation may reflect differences in the conditions of the elderly patients and level of attention (or complexity of care), as well as methodological differences, especially the methods and/or software used to identify DDIs. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42018096720.