OBJECTIVES: The study aim was to examine how Registered Nurses identify and respond to deteriorating patients during in-hospital simulation exercises. DESIGN: Mixed methods study using simulated actors. SETTING: A rural hospital in Victoria, Australia. PARTICIPANTS: Thirty-four Registered Nurses each completed two simulation exercises. METHODS: Data were obtained from the following sources: (a) Objective Structured Clinical Examination (OSCE) rating to assess performance of Registered Nurses during two simulation exercises (chest pain and respiratory distress); (b) video footage of the simulation exercises; (c) reflective interview during participants' review of video footage. Qualitative thematic analysis of video and interview data was undertaken. RESULTS: Themes generated from the data were: (1) exhausting autonomous decision-making; (2) misinterpreting the evidence; (3) conditioned response; and (4) missed cues. Assessment steps were more likely to be omitted in the chest pain simulation, for which there was a hospital protocol in place. CONCLUSIONS: Video review revealed additional insights into nurses' decision-making that were not evident from OSCE scoring alone. Feedback during video review was a highly valued component of the simulation exercises.