The simultaneous use of multiple drugs—termed ‘polypharmacy’—is often required to manage multiple physiological and biological changes and the interplay between chronic disorders that are expected to increase in association with ageing. However, by increasing the number of medications consumed, the risk of undesirable medication reactions and drug interactions also increases exponentially. Hence, knowledge of the prevalence of polypharmacy and the risk of potentially serious drug–drug interactions (DDIs) in elderly patients should be considered a key topic of interest for public health and health care professionals.Methods:Prescription and demographic data were collected from the electronic files of patients who were aged ≥ 65 years and attended Al-Noor Hospital in Makkah, Saudi Arabia, between 2015 and 2022. The Lexicomp®electronic DDI-checking platform was used to evaluate the patients’ medication regimens for any potential drug interactions.Results:A total of 259 patients were included in the study. The prevalence of polypharmacy among the cohort was 97.2%: 16 (6.2%) had minor polypharmacy, 35 (13.5%) had moderate polypharmacy, and 201 (77.6%) had major polypharmacy. Of the 259 patients who were taking two or more medications simultaneously, 221 (85.3%) had at least one potential DDI (pDDI). The most frequently reported pDDI under category X that should be avoided was the interaction between clopidogrel and esomeprazole and was found in 23 patients (18%). The most frequently reported pDDI under category D that required therapeutic modification was the interaction between enoxaparin and aspirin, which was found in 28 patients (12%).Conclusions:It is often necessary for elderly patients to take several medications simultaneously to manage chronic diseases. Clinicians should distinguish between suitable, appropriate and unsuitable, inappropriate polypharmacy, and this criterion should be closely examined when establishing a therapeutic plan.