BackgroundIt is essential that nurses quickly learn the proper methods for preventing and controlling nosocomial infection and managing intensive care patients during the COVID-19 pandemic, including the donning and doffing of personal protective equipment (PPE). Virtual reality (VR) simulation offers the advantage of learning in a safe environment with a sense of realism similar to that of an actual clinical setting and has been reported to enhance self-efficacy in infection control, safety performance, and learning satisfaction among students.ObjectiveThis study aims to develop a virtual reality infection control simulation (VRICS) program regarding donning and doffing of PPE and respiratory care for pediatric patients admitted to an isolation unit for COVID-19 and to identify the effects of the program on PPE knowledge, infection control performance, and self-efficacy for nursing students. Additionally, the realism of the VRICS program and the students’ level of satisfaction with the program were assessed.MethodsThis was a quasi-experimental study based on a controlled pretest-posttest design. Third- and fourth-year nursing students were divided into an experimental group (n=25) who participated in a VRICS program and a control group (n=25) with no participation. Data were collected from November 13 to December 10, 2021, and analyzed using descriptive statistics and the t test, paired t test, Mann-Whitney U test, and Wilcoxon matched-pair signed-rank test. The VRICS program consisted of a prebriefing, including direct practice of donning and doffing PPE, VR simulation, and debriefing. The VR simulation comprised 3 sessions: donning and inspection of PPE in the dressing room before entering the negative-pressure isolation unit; assessing for suction care, nasopharyngeal suctioning, and checking of COVID-19 patients in the negative-pressure isolation unit; and doffing PPE in the dressing room. The total execution time for the program was 180 min.ResultsCompared with the control group, the experimental group showed significantly greater improvements in PPE knowledge (z=–3.28, P<.001), infection control performance (t48=4.89, P<.001), and self-efficacy (t36.2=4.93, P<.001). The experimental group’s mean scores for realistic immersion and learner satisfaction were 4.49 (SD 0.50) points and 4.75 (SD 0.38) points (on a 5-point Likert scale), respectively.ConclusionsThe VR simulation training program involving pediatric COVID-19 patients combined skills training effectively and enhanced theoretical knowledge, respiratory care skills, and infectious disease preparedness. Thus, it could be applied to training nurses to respond more effectively to public health situations involving infectious diseases, including the COVID-19 pandemic.