Introduction: Virtual reality-based simulation is an educational tool that has been proven to increase participants’ self-perceived, confidence, and skill. However, the use of VR is associated with virtual reality sickness (VRS). The purpose of this study is to determine related factors of VRS in an emergency setting simulation-based training, hence providing information and mitigation plan to enhance and optimize learning outcomes. Method: We developed multiplayer VR simulation in Traumatic Brain Injury and Local Anaesthetic Systemic Toxicity emergency. Seventy-five medical doctors voluntarily partake in the VR simulation. Throughout the simulation and its aftermath, participants were carefully monitored and observed. Additionally, they were questioned regarding their experience of VRS using the Simulation Sickness Questionnaire (SSQ) instrument. Result: The incidence of virtual reality sickness was found to be 57.3% and is significantly associated with male gender, myopia, astigmatism, and the use of stationary VR mode (p<0.05). The mean SSQ score for nausea, oculomotor, disorientation, and total score component is 5.97 (standard deviation (SD): 6.4), 6.26 (SD 6.5), 125.6 (SD 132), and 9.03 (SD 9.5), respectively. There were 16% of participant experiencing severe symptoms of VRS. Conclusion: Male gender, myopia, astigmatism, and the use of stationary VR mode were related with incidence of virtual reality sickness. VR activities in either room-scale or walking mode and appropriate correction of any refractive disorders are pivotal to prevent VRS in VR simulation training. © The Author(s) 2024.