ABSTRACT Aims: To estimate the prevalence of polypharmacy among community-dwelling adults in the UK and determine its association with mortality, hospitalization, adverse drug reactions and falls at one and five years. Method: A retrospective cohort study was carried out using 1000 patients aged 75 years and above from the Clinical Practice Research Datalink. The follow-up periods for one and five years were January 2010 to December 2010, and January 2010 to December 2014 respectively. Sociodemographic and clinical variables were retrieved using medical and product codes. The association between polypharmacy and mortality, falls, adverse drug reactions, and hospitalization was determined using Cox regression analysis while confounding for age, sex, Charlson’s Comorbidity Index, potentially inappropriate medicines, previous hospitalization, and previous falls. Results: The prevalence of polypharmacy was 47%. Adjusted hazard ratios with their 95% confidence intervals for polypharmacy and outcomes at five years were mortality 1.60(1.3-2.0), hospitalization 1.49(1.3-1.7), falls 1.49(0.9-2.4), and adverse drug reactions 0.97(0.5-1.8). The results for the one-year analysis were mortality 2.37(1.4-3.9), hospitalization 2.47(1.4-4.3), and falls 0.37(0.03-4.0). The result for adverse drug reactions was omitted. Conclusion: Polypharmacy was found to be an independent risk factor for mortality and hospitalization, but not falls or adverse drug reactions.