Objective This study aims to teach and evaluate the actual application effect of the simulation system for putting on and taking off personal protective equipment (PPE) developed by virtual reality technology. Methods A total of 64 front-line medical staff were randomly divided into a control group and a trial group, with 32 in each group. The control group adopted the conventional PPE donning and doffing process teaching mode, and the experimental group was taught based on the virtual reality simulation system. The effects between the two groups were analyzed and compared, and the experience of the test group was investigated. Results The experimental group used less time to select the venue and items, scored higher on the wearing and taking off effect, and had less contamination quantity and area than the control group (P<0.05). 93.75% of the test group members had a good or excellent experience in using the virtual reality simulation system. Conclusion Virtual reality technology can break limitations of materials and venues in PPE teaching and improve the training effect.