BackgroundPolypharmacy is frequently used as a quality indicator for older adults in Residential Aged Care Facilities (RACFs) and is measured using a range of definitions. The impact of data source choice on polypharmacy rates and the implications for monitoring and benchmarking remain unclear. We aimed to determine polypharmacy rates (≥9 concurrent medicines) by using prescribed and administered data under various scenarios, leveraging electronic data from 30 RACFs.MethodA longitudinal cohort study of 5662 residents in New South Wales, Australia. Both prescribed and administered polypharmacy rates were calculated biweekly from January 2019 to September 2022, providing 156 assessment times. 12 different polypharmacy rates were computed separately using prescribing and administration data and incorporating different combinations of items:medicines and non-medicinal products,any medicinesandregular medicinesacross four scenarios: no, 1-week, 2-week and 4-week look-back periods. Generalised estimating equation models were employed to identify predictors of discrepancies between prescribed and administered polypharmacy.ResultsPolypharmacy rates among residents ranged from 33.9% using data on administeredregular medicineswith no look-back period to 63.5% using prescribedmedicines and non-medicinal productswith a 4-week look-back period. At each assessment time, the differences between prescribed and administered polypharmacy rates were consistently more than 10.0%, 4.5%, 3.5% and 3.0%, respectively, with no, 1-week, 2-week and 4-week look-back periods. Diabetic residents faced over two times the likelihood of polypharmacy discrepancies compared with counterparts, while dementia residents consistently showed reduced likelihood across all analyses.ConclusionWe found notable discrepancies between polypharmacy rates for prescribed and administered medicines. We recommend a review of the guidance for calculating and interpreting polypharmacy for national quality indicator programmes to ensure consistent measurement and meaningful reporting.