PURPOSE: This study analyses the relationship between medication use and frailty by considering the quantity of medications prescribed (polypharmacy) and the quality of medication prescribing (according to French criteria for Potentially Inappropriate Medications-PIMs) in people aged 65 and over. METHODS: This is a cross-sectional study based on the data from a nationally representative study about health and use of healthcare resources in France (ESPS 2012). The number of frailty criteria was assessed among exhaustion, unintentional weight loss, muscle weakness, impaired mobility, and low level of physical activity. Polypharmacy and PIMs were assessed from the data of reimbursement by the National Health Insurance over the whole year 2012. PIMs were defined according to the Laroche list plus additional criteria dealing with inappropriate prolonged use of medications. The analyses used Poisson regression models, with the number of frailty criteria as dependent variable. RESULTS: The study population was composed of 1003 women and 887 men, of mean age 74.7 +/- 7.4 years. Polypharmacy (5 to 9 drugs) and excessive polypharmacy (≥10 drugs) were reported in 42.9 and 27.4% of the study population, respectively, while 46.7% of the study population received at least one PIM during the year 2012. Polypharmacy and PIMs were both associated with the number of frailty criteria in models adjusted for socio-demographic and health characteristics of the participants. The prescription of anticholinergic medications was the only PIM that remained significantly associated with the number of frailty criteria after adjustment for polypharmacy. CONCLUSIONS: Polypharmacy and use of anticholinergic medications are independently associated with frailty in old people.