Purpose <p>Virtual reality (VR) may offer training advantages over mannequin-based high-fidelity simulation (HFS), but data are lacking. We sought to investigate whether VR is noninferior to HFS in teaching nontechnical skills to anesthesiology trainees.</p> Methods <p>We conducted a sequential randomized controlled noninferiority trial to compare two simulation crisis management scenarios in 31 anesthesiology trainees. Scenario #1 was delivered either as a VR or as HFS. After 3 weeks, all participants underwent scenario #2, delivered only as HFS. We set a noninferiority margin of 0.6 for the overall improvement on the Ottawa Global Rating Scale (O-GRS), a crisis resource management scale, in scenario #2 between the two groups. As secondary outcomes, we compared changes in the Anaesthetists’ Non-technical Skills (ANTS) scale and the Managing Emergencies in Paediatric Anaesthesia Global Rating Scale (MEPA-GRS) between the two groups. We also evaluated the VR module using the VR Sickness Questionnaire (VRSQ), the System Usability Scale (SUS), the Technology Acceptance Model, and a feedback survey.</p> Results <p>During scenario #2, VR was noninferior to HFS regarding the overall O-GRS improvement (mean difference [upper bound 97.5% confidence interval], −0.4 [0.5]). Likewise, the VR and HFS groups showed no significant differences in ANTS and MEPA-GRS during scenario #2. In scenario #1, the VR and HFS groups’ O-GRS, ANTS, and MEPA-GRS scores were comparable. The VR module reported a low VRSQ score (median [interquartile range (IQR)], 8.3 [4.2–15.8]), high-marginal SUS (median [IQR], 65 [62.5–80.0]), and feedback comparable to HFS.</p> Conclusions <p>Virtual reality was noninferior to HFS in teaching anesthesiology nontechnical skills, and it was well tolerated and perceived.</p> Study registration <p>ClinicalTrials.gov (<a href="https://clinicaltrials.gov/study/NCT05041049?intr=NCT05041049&amp;rank=1">NCT05041049</a>); first submitted 10 September 2021.</p>