The objective of the study was to investigate the prevalence of, and factors associated with, polypharmacy in long-term care facilities (LTCFs).MEDLINE, EMBASE, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library were searched from January 2000 to September 2014. Primary research studies in English were eligible for inclusion if they fulfilled the following criteria: (1) polypharmacy was quantitatively defined, (2) the prevalence of polypharmacy was reported or could be extracted from tables or figures, and (3) the study was conducted in a LTCF. Methodological quality was assessed using an adapted version of the Joanna Briggs Institute Critical Appraisal Checklist.Forty-four studies met the inclusion criteria and were included. Polypharmacy was most often defined as 5 or more (n = 11 studies), 9 (n = 13), or 10 (n = 11) medications. Prevalence varied widely between studies, with up to 91%, 74%, and 65% of residents taking more than 5, 9, and 10 medications, respectively. Seven studies performed multivariate analyses for factors associated with polypharmacy. Positive associations were found for recent hospital discharge (n = 2 studies), number of prescribers (n = 2), and comorbidity including circulatory diseases (n = 3), endocrine and metabolic disorders (n = 3), and neurological motor dysfunctioning (n = 3). Older age (n = 5), cognitive impairment (n = 3), disability in activities of daily living (n = 3), and length of stay in the LTCF (n = 3) were inversely associated with polypharmacy.The prevalence of polypharmacy in LTCFs is high, varying widely between facilities, geographical locations and the definitions used. Greater use of multivariate analysis to investigate factors associated with polypharmacy across a range of settings is required. Longitudinal research is needed to explore how polypharmacy has evolved over time.