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Objective: To identify factors associated with appropriate knowledge about the indications for drugs prescribed to older patients on polypharmacy., Design: Cross-sectional study., Method: In a primary care setting, patients aged 60 years and over who were taking five or more prescribed drugs simultaneously were asked about their medication by conducting home interviews and postal questionnaires. Multiple logistic regression analysis was used to evaluate the association between medication knowledge and explanatory variables such as medication use, sex, age, residential status and educational level., Results: Seven hundred and fifty-four participants, mean age 73.2 years, reported an average daily intake of nine (SD 3.0) prescribed drugs. Only 15% of the patients were able to recall the indication for each of their prescribed drugs. Variables that were negatively associated with correct reporting of all indications were: taking many prescribed drugs (≥ 10 vs. ≤ 5 drugs: odds ratio (OR) 0.05), age 80 years or over (vs. 60-69 years: OR 0.47) and male sex (vs. females: OR 0.53). Patients living with a partner were more knowledgeable than patients living alone (OR 2.11). We did not find an association with educational level., Conclusion: Among older patients using five or more prescribed drugs, there was little understanding of the indications for their drugs, especially among patients taking the highest number of drugs, patients aged 80 years or over, and men. Patients living independently with a partner were more knowledgeable than others.