We aimed to describe the burden represented by potentially inappropriate medications (PIMs) in chronic polypharmacy in France. We conducted a nationwide cross-sectional study using data from the French National Insurance databases. The study period was from 1 January 2016 to 31 December 2016. Chronic drug use was defined as uninterrupted daily use lasting ?6 months. Chronic polypharmacy was defined as the chronic use of ?5 medications, and chronic hyperpolypharmacy as the chronic use of ?10 medications. For individuals aged ?65 (older adults), PIMs were defined according to the Beers and Laroche lists, and for individuals aged 45-64 years (middle-aged) PIMs were defined according to the PROMPT (Prescribing Optimally in Middle-aged People's Treatments) list. Among individuals with chronic polypharmacy, 4009 (46.2%) middle-aged and 18,036 (64.8%) older adults had at least one chronic PIM. Among individuals with chronic hyperpolypharmacy, these figures were, respectively, 570 (75.0%) and 2544 (88.7%). The most frequent chronic PIM were proton pump inhibitors (43.4% of older adults with chronic polypharmacy), short-acting benzodiazepines (older adults: 13.7%; middle-aged: 16.1%), hypnotics (6.1%; 7.4%), and long-acting sulfonylureas (3.9%; 12.3%). The burden of chronic PIM appeared to be very high in our study, concerning almost half of middle-aged adults and two-thirds of older adults with chronic polypharmacy. Deprescribing interventions in polypharmacy should primarily target proton pump inhibitors and hypnotics.< Réduire