BACKGROUND: In 2011, the EU Directive on Patients' Rights in Cross Border Healthcare was approved, including a regulation on mutual recognition of prescriptions. OBJECTIVE: To compare current national policies and practices on prescribing and dispensing, prescription-only medicines (POMs) in European countries in order to identify differences which could, challenge acceptance across borders. METHODS: Semi-structured interviews with 37 national stakeholders were carried out. Furthermore, data on policies for prescribing and dispensing POMs were gathered based on desk research, and, contacts with relevant authorities via a purposely designed questionnaire. RESULTS: Important differences exist regarding: (1) information requirements for prescriptions to be, legally valid, (2) generic and international non-proprietary name (INN) policies and (3) professionals, legally allowed to prescribe POMs. Moreover, there is a lack of EU-wide access to key information for, validating prescriptions, recognizing the equivalence of products or identifying authorised prescribers. CONCLUSION: Differences in legislation and its application across Europe pose important challenges to be, addressed by policy makers with appropriate actions: (1) a prescribed product may not be dispensed, to a patient who needs it, (2) an inappropriate product (or inappropriate instructions) could be, provided and (3) POMs could be dispensed and consumed or sold, based on false prescriptions.