OBJECTIVE: To investigate the effects and challenges of being a simulated patient (SP) in a high-stakes clinical examination context in a regional setting. DESIGN: Mixed methods, using a written survey, focus groups, and a retrospective postal survey. SETTING: A university clinical school in a Victorian regional city. PARTICIPANTS: Nineteen SP volunteers (from an existing database of 55 people) who had been involved in mid-year, summative Objective Structured Clinical Examination (OSCE) role-play performances. MAIN OUTCOME MEASURES: Challenges of the OSCE role-play experience and the reported effects on SPs. The implications of these factors have an impact on the sustainability of SP programs in regional settings. RESULTS: Physical and emotional effects like exhaustion were reported, as well as empathy and concern for the medical students. The retrospective postal survey indicated that the SPs had no long-term negative effects from their high-stakes examination experiences. Participants also reported that a level of decision making and improvisation was needed in the performance of their OSCE role plays. CONCLUSIONS: Our study reveals the complexity and demands on SPs in performing in high-stakes clinical examinations. The results highlight that SP roles involve more than the transfer of scripted information. SPs should be considered as members of the examination team when preparing and implementing high-stakes examinations to assist in maintaining standardised performance during and across OSCE role plays. Relationships between SPs and educational institutes need to be nurtured to ensure that the ability to continue high-stakes OSCEs in a regional setting is maintained.