PURPOSE: The quality of drug therapy is an important issue for nursing homes. This study aimed to assess the prevalence of polypharmacy and potentially inappropriate medications (PIMs) in a large sample of nursing home residents by using the data recorded during the preparation of pill dispensers. METHODS: This is a cross-sectional study that included 451 nursing homes across France. Information about the medications received by the 30,702 residents (73.8% women) living in these nursing homes was extracted from the system that assists in the preparation of pill dispensers in pharmacies. The anonymized database included age, sex, and medications prescribed to residents, as well as nursing home characteristics (capacity, legal status). Factors associated with excessive polypharmacy (≥10 different drugs) and PIMs according to the Laroche list were studied using multilevel regression models. RESULTS: The average number of drugs prescribed was 6.9 ± 3.3, and excessive polypharmacy concerned 21.1% of the residents (n = 6468). According to the Laroche list, 47.4% of residents (n = 14,547) received at least one PIM. Benzodiazepines (excessive doses, long-acting benzodiazepines, and combination of benzodiazepines) and anticholinergic medications (hydroxyzine, cyamemazine, alimemazine) accounted for a large part of PIMs. Individual characteristics (age, gender) influenced the risk of receiving PIMs whereas nursing home characteristics (capacity, legal status) influenced the risk of excessive polypharmacy. CONCLUSIONS: This study shows that polypharmacy and PIMs remain highly prevalent among nursing home residents. Main PIMs concerned psychotropic and anticholinergic medications.