OBJECTIVE: Pharmacological treatment of older adults with cognitive impairment represents a challenge for prescribing physicians, and polypharmacy is common in these complex patients. The aim of the current study is to assess prevalence and factors related to polypharmacy in a sample of nursing home (nursing home) residents with advanced cognitive impairment. METHODS: We conducted a cross-sectional analysis of 1449 nursing home residents with advanced cognitive impairment participating to the Services and Health for Elderly in Long Term Care (SHELTER) project, a study collecting information on residents admitted to 57 nursing home in eight countries. Data were collected using the International Resident Assessment Instrument (InterRAI) for long-term care facilities. Polypharmacy status was categorized into three groups: nonpolypharmacy (zero to four drugs), polypharmacy (five to nine drugs), and excessive polypharmacy (≥10 drugs). RESULTS: Polypharmacy was observed in 735 residents (50.7%) and excessive polypharmacy was seen in 245 (16.9%). Compared with nonpolypharmacy, excessive polypharmacy was associated directly with ischemic heart disease (odds ratio [OR], 3.68; 95% confidence interval [CI], 2.01-6.74), diabetes mellitus (OR, 2.66; 95% CI; 1.46-4.84), Parkinson's disease (OR, 2.84; 95% CI, 1.36-5.85), gastrointestinal symptoms (OR, 1.20; 95% CI, 1.43-3.39), pain (OR, 3.12; 95% CI, 1.99-4.89), dyspnea (OR, 2.57; 95% CI, 1.31-5.07), and recent hospitalization (OR, 2.56; 95% CI, 1.36-5.85). An inverse relation with excessive polypharmacy was shown for age (OR, 0.74; 95% CI, 0.59-0.93), activities of daily living disability (OR, 0.79; 95% CI, 0.63-0.99) and presence of a geriatrician on the nursing home staff (OR, 0.36; 95% CI, 0.20-0.64). CONCLUSION: Polypharmacy and excessive polypharmacy are common among nursing home residents with advanced cognitive impairment. Determinants of polypharmacy status includes not only comorbidities, but also specific symptoms, age, and functional status. A geriatrician in the facility is associated with lower prevalence of excessive polypharmacy.