Background Discharge prescribing error is common. Little is known about whether it persists post-discharge. Objective To explore the relationship between discharge prescribing error and post-discharge medication error. Setting This was a prospective observational study (March-May 2013) at an adult academic hospital in Ireland. Method Patients using three or more chronic medications pre-admission, with a clinical pharmacist documented gold-standard pre-admission medication list, having a chronic medication stopped or started in hospital and discharged to home were included. Within 10-14 days after discharge a gold standard discharge medication was prepared and compared to the discharge prescription to identify differences. Patients were telephoned to identify actual medication use. Community pharmacists, general practitioners and hospital prescribers were contacted to corroborate actual and intended medication use. Post-discharge medication errors were identified and the relationship to discharge prescribing error was explored. Main outcome measured Incidence, type, and potential severity of post-discharge medication error, and the relationship to discharge prescribing. Results Some 36 (43 %) of 83 patients experienced post-discharge medication error(s), for whom the majority (n = 31, 86 %) were at risk of moderate harm. Most (58 of 66) errors were discharge prescribing errors that persisted post-discharge. Unintentional prescription of an intentionally stopped medication; error in the dose, frequency or formulation and unintentional omission of active medication are the error types most likely to persist after discharge. Conclusion There is a need to implement discharge medication reconciliation to support medication optimisation post-hospitalisation.