Aim <p>The aim of this repeated cross-sectional study was to estimate polypharmacy prevalence and trends in Australian adults between 2013 and 2024.</p> Methods <p>Dispensing records of medicines subsidised by the Australian Pharmaceutical Benefits Scheme (PBS) were analysed for a nationally representative 10% sample of PBS-eligible beneficiaries.</p> Outcomes <p>The outcomes for this study were annual polypharmacy and hyperpolypharmacy prevalence, defined as ≥5 and ≥10 regular medicines, respectively, and average annual percentage change (AAPC), overall and by gender-stratified age groups. These groups are defined broadly as adult (18–64 years) and older adult (≥65 years), and as younger adulthood (18–39 years), middle (40–64 years), early older (65–84 years) and later older (85+ years) age.</p> Results <p>Polypharmacy prevalence rose from 8.0% in 2013 to 9.2% (AAPC+1.4%), with two million Australians exposed in 2024. Although prevalence was initially higher among women, by 2024 men had surpassed women from middle age onward. Increasing AAPC was observed among adult and older adult men (+1.0%, +1.3%), while remaining stable among women. Finer age strata showed growth among men in middle, early older, and later older age (+1.7%, +1.0%, +3.4%) and divergent trends among women, with increases in younger adulthood (+1.8%) and declines in early older age (− 0.7%).</p> Conclusion <p>Shifting gender trends appear driven by stabilising or declining prevalence among women alongside sustained growth among men. By 2024, men exceeded women from middle age onward, suggesting a changing prescribing landscape. These patterns highlight the need for targeted interventions, and gender-stratified monitoring to ensure&#xa0;prescribing is appropriate. The long-term consequences of increasing polypharmacy in younger and middle-aged adults remain unclear and warrant further investigation.</p>