BACKGROUND: Virtual reality (VR) is an interesting and promising way to teach cardiopulmonary resuscitation (CPR) to adult laypersons as its high immersive characteristics could improve the level of skills and acquired knowledge in learning basic life support (BLS). METHODS: This systematic review assesses current literature about BLS training with VR and its possible effect on CPR-quality parameters, self-efficacy, perceived learning, and learners' satisfaction and short and long-term patients' outcome. We screened the Cochrane Library, PubMed, CINAHL, MEDLINE Ovid, Web of Science, and Scopus databases and included only clinical trials and quasi-experimental studies published from inception to October 1, 2021, which analyzed adult laypersons' BLS training with the use of VR. Primary outcomes were CPR parameters (chest compression rate and depth, Automated External Defibrillator use). Secondary outcomes were self-efficacy, perceived learning and learners satisfaction, and patients' outcomes (survival and good neurologic status). The risk of bias of included study was assessed using the Cochrane Handbook for Systematic Reviews of Interventions tool to evaluate randomized control trials and the transparent reporting of evaluations with nonrandomized designs checklist for nonrandomized studies. RESULTS: After full article screening, 6 studies were included in the systematic review (731 participants) published between 2017 and 2021. Because of the heterogeneity of the studies, we focused on describing the studies rather than meta-analysis. The assessment of the quality of evidence revealed overall a very low quality. Training with VR significantly improved the rate and depth of chest compressions in 4 out of 6 articles. VR was described as an efficient teaching method, exerting a positive effect on self-efficacy, perception of confidence, and competence in 2 articles. CONCLUSION: VR in BLS training improves manual skills and self-efficacy of adult laypersons and may be a good teaching method in a blended learning CPR training strategy. VR may add another way to divide complex parts of resuscitation training into easier individual skills. However, the conclusion of this review suggests that VR may improve the quality of the chest compressions as compared to instructor-led face-to-face BLS training.