Abstract Background Polypharmacy, the use of 5 or more medications simultaneously, favors the risk of adverse drug events, drug interactions, potentially inappropriate medication (PIM), hospitalizations, falls, frailty, and mortality. This analysis presents the prevalence of polypharmacy and associated factors in people aged 66+ years living in Germany. Methods Data from the nationally representative Study on Health of Older People in Germany (Gesundheit 65+) conducted between 2021-2023 by the Robert Koch Institute, was analyzed. All medicines used, prescribed and over-the-counter, in the 7 days before the interview were documented and classified into anatomical therapeutic chemical codes. Weighted prevalences and associated factors for polypharmacy are presented. Results 96% of the sample (N = 1,474) took at least 1 medication in the 7 days before the interview. Of these, 39% took up to 4 medications, 39% 5-9 and 22% 10+. The overall prevalence of polypharmacy was 61% (95%CI 58-65%) and was significantly higher in women (64%) than in men (59%). Polypharmacy increased with age, from 52% in the age group 66-74 (53% in men, 51% in women), 66% in the age group 75-84 (63% in men, 69% in women) to 81% in the age group 85 + (72% in men, 86% in women). People with low educational level had a polypharmacy prevalence of 63% (58% in men, 66% in women) compared to 56% (55% in men, 58% in women) in those with high educational level. Severe difficulties in organizing daily medication intake were reported in 1% of people taking up to 4 medicines, in 4% of people taking between 5-9 medicines and in 16% of people taking 10+. The prevalence of PIM increased with the number of medicines used: 13% in 1-4 medicines, 31% in 5-9 medicines, and 53% in 10+ medicines. Conclusions Polypharmacy was more frequent in women, older age groups and in people with low educational level. It was associated with increased difficulty in organizing medication intake and with PIM use. Key messages • Polypharmacy is very common, affecting more women, older age groups, people with a low educational level and is associated with PIM use. • Strategies to promote appropriate medication use are needed.