Background: Polypharmacy increases with age and is associated with serious health and economic costs. This study reports changes over a decade in medication-use patterns and polypharmacy, in Israeli community-dwelling older adults aged ≥ 65 years. Methods: Demographic and health data from two representative national health cross-sectional surveys – MABAT ZAHAV 1 (MZ1) in 2005–2006, and MZ2 in 2014–2015 were analyzed. Polypharmacy was defined as use of ≥ 5 medications. Risk factors for polypharmacy were estimated by multivariable logistic regression with adjusted odds ratios (aOR) and their 95% confidence intervals (CI). Results: Self-reported data on medications taken were available for 1647 participants (91.5%) in MZ1, and for 833 participants (80.2%) in MZ2, 55% women, and about 20% aged ≥ 80, in both surveys. The prevalence of polypharmacy was significantly lower in MZ2 than in MZ1: 64.2% versus 56.3%, p =.0001; with an aOR (95%CI) of 0.64 (0.52, 0.80). The most commonly taken drugs were for hypertension (27.0%, 25.3%), dyslipidemia (9.7%, 12.4%) and anticoagulation (9.2%, 9.8%). For approximately 10% of drugs, indications were either unknown or incorrect. Polypharmacy was significantly associated with poor self-health assessment 2.47 (1.99, 3.06), ≥ 4 versus 1–3 chronic illnesses 6.36 (3.85, 10.50), and age ≥ 80 versus younger 1.72 (1.32, 2.24). Similar associations were observed with major polypharmacy of ≥ 8 medications. Conclusion: Polypharmacy, although reduced in the last decade, requires constant attention, especially concerning lack of knowledge of indications which leads to poor adherence and adverse side effects. Health-care teams should carry out regular medicine reconciliation in at-risk elderly patients.