Aims Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes, and poor information transfer between hospital and primary care. The aim of this study was to investigate the incidence, severity, preventablitiy and cost of medication-relate harm (MRH) in older adults in England post-discharge. Methods An observational multicentre prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for eight weeks by senior pharmacists, using 3 data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associate health service utilisation. Results Four hundred and thirteen participants (37%) experienced MRH (556 MRH events per 1000 discharges). Three hundred and thirty-six (81%) cases were serious, and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n=158, 25%) and neurological (n=111, 18%). Medicine classes associate with the highest risk of MRH were opiates, antibiotics, and benzodiazepines. Three hundred and twenty-eight (79%) participants with MRH sought healthcare over the eight-week follow-up. The incidence of MRH associated hospital readmission was 78 per 10000 discharges. Post-dischare MRH in older adults is estimated to cost the National Health Service £396 million annually, f which £243 million is potentially preventable. Conclusions MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.