Objective: To examine how the setting in in situ simulation (ISS) and off-site simulation (OSS) in simulation-based medical education affects the perceptions and learning experience of healthcare professionals. Design: Qualitative study using focus groups and content analysis. Participants: Twenty-five healthcare professionals (obstetricians, midwives, auxiliary nurses, anaesthesiologists, a nurse anaesthetist and operating theatre nurse) participated in four focus groups and were recruited due to their exposure to either ISS or OSS in multidisciplinary obstetric emergencies in a randomised trial. Setting: Departments of obstetrics and anaesthesia, Rigshospitalet, Copenhagen, Denmark. Results: Initially participants preferred ISS, but this changed after the training when the simulation site became of less importance. There was a strong preference for simulation in authentic roles. These perceptions were independent of the ISS or OSS setting. Several positive and negative factors in simulation were identified, but these had no relation to the simulation setting. Participants from ISS and OSS generated a better understanding of and collaboration with the various health professionals. They also provided individual and team reflections on learning. ISS participants described more experiences that would involve organisational changes than the OSS participants did. Conclusions: Many psychological and sociological aspects related to the authenticity of the learning experience are important in simulation, but the physical setting of the simulation as an ISS and OSS is the least important. Based on these focus groups OSS can be used provided that all other authenticity elements are taken into consideration and respected. The only difference was that ISS had an organisational impact and ISS participants talked more about issues that would involve practical organisational changes. ISS and OSS participants did, however, go through similar individual and team learning experiences.