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Background: With the aging of the population and the increase in chronic diseases, there is an inherent risk of polypharmacy and inappropriate medication use. This study aimed to determine the prevalence and incidence of potentially inappropriate medication use and its correlation with polypharmacy., Methods: This was a retrospective, population-based cohort study among patients ≥ 65 years hospitalized at The National University Hospital of Iceland from 2010-2020. Data on medication usage were retrieved from the National Prescription Medicine Registry. Based on the number of medications filled in the year prior to admission and post-discharge, participants were categorized as non-polypharmacy (<5), polypharmacy (5-9), and hyper-polypharmacy (≥10). The prevalence and incidence of potentially inappropriate medication use was assessed based on the 2019 Beers criteria. Regression models were used to correlate sociodemographic, clinical, and pharmacoepidemiologic variables and the odds of new potentially inappropriate medication use., Results: The cohort comprised 55,859 patients (48.5% male) with a median [interquartile range] age of 80 [73-86] years. The prevalence of inappropriate medication use in the year preceding admission was 34.0%, 77.7%, and 96.4% for patients with non-polypharmacy, polypharmacy, and hyper-polypharmacy, respectively. The incidence of new potentially inappropriate medication use was 46.7% (95% confidence interval 45.6%-47.6%) among those with no potentially inappropriate medication use pre-admission. Factors associated with higher odds of new potentially inappropriate medication use after discharge were the use of multi-dose dispensing services, dementia, polypharmacy, and hyper-polypharmacy., Conclusions: An increased emphasis is needed to review and reevaluate the appropriateness of medication use among the older population in internal medicine., (Copyright © 2024 Elsevier Inc. All rights reserved.)