BACKGROUND: Polypharmacy is an important concern for patient safety and has been associated with increased adverse drug reactions, hospitalization and mortality in the elderly. OBJECTIVE: In light of the above, the present study aimed to assess the major characteristics associated with polypharmacy (≥ 4 drugs) in a larger population of apparently healthy older subjects over 60 years. STUDY-DESIGN: Cross-sectional study. SETTING: The preventive medical center (CMP) in Nancy. PARTICIPANTS: 2,545 volunteers (1,175 women, 1,370 men) aged 60 years and older (66 ± 4.8 years) were included from the Senior health examination study. MEASUREMENTS: All subjects underwent clinical, biological examinations. Sociodemographic data, practice of regular physical activity and drug intake data were collected. A self-administered questionnaire of health status, psychological status and questions regarding falls were collected. RESULTS: The prevalence of polypharmacy in this study was 29.9%. The number of drugs in polymedicated people was 5.67 ± 1.82 versus 1.32 ± 1.11 in non polymedicated people; p≤0.01. Multivariate analyses identified 6 independent variables associated with polypharmacy: age over 65 years (OR = 1.58 95% CI: [1.05 - 2.38]; p = 0.03), poor self-perceived health status (2.79 [1.80 - 4.31]; p ≤ 0,01), history of falls (1.66 [1.02 - 2.71]; p = 0.04), lack of a physical activity (1.50 [1.001 - 2.26]; p = 0.049), metabolic syndrome (3.17 [1.95 - 5.15]; p ≤ 0,01), low or medium education level (2.20 [1.24 - 4.30]; p = 0.02). CONCLUSION: Among community-dwelling people aged 60 years and over, in addition to the presence of several diseases and advanced age, the psychological and socio-educative factors may influence drug intake and polypharmacy in the elderly. Physicians should be take into account these considerations before issuing any prescriptions and review all medications used at every visit to avoid unnecessary addictions or dangerous drug-drug interactions.