OBJECTIVES: We sought to evaluate the prevalence of polypharmacy, and to determine patient characteristics that are predictive of exposure to polypharmacy in the elderly population of Emilia-Romagna, Italy. METHODS: We conducted a retrospective cohort study of the 2007 Emilia-Romagna outpatient pharmacy database linked with patient information available from a demographic file of approximately 1 million Emilia-Romagna residents aged ≥65 years. The cohort was comprised of 887,165 elderly patients who had at least one prescription filled during the study year. Using the World Health Organization's Defined Daily Dose (DDD) to determine the duration of treatment for a given drug, we defined a polypharmacy episode as overlapping treatment with 5 or more medications occurring for at least one day. The prevalence of polypharmacy was measured together with patient characteristics found to be predictive of polypharmacy exposure. RESULTS: A total of 349,689 elderly in the population (39.4%) were exposed to at least one episode of polypharmacy. The prevalence of polypharmacy substantially increased with age, (32.7% for those ages 65-74, over 45% for those ages 75+). Over 35% of those exposed to polypharmacy were exposed for 101 or more days of the year. The top three classes of medications involved in polypharmacy were antithrombotics, peptic ulcer disease and gastro-esophageal reflux disease agents, and angiotensin-converting enzyme inhibitors. Compared to unexposed subjects, elderly exposed to polypharmacy were older, were more likely to be male, and had a greater number of chronic conditions. CONCLUSIONS: This study provides evidence that the prevalence of polypharmacy in the elderly in Emilia-Romagna is substantial. Educational programs targeting primary care physicians should be developed to make them aware of the magnitude of polypharmacy phenomenon, as well of patient characteristics associated with polypharmacy to ensuring safe, effective, and appropriate use of medication in the elderly population.