This study aimed to evaluate the effect of virtual reality simulation in nursing education in five domains: knowledge, skill performance, self-confidence, self-efficacy, and satisfaction. Randomized controlled trials were obtained from the databases SCOPUS, Web of Science, PubMed, and EBSCO from inception until September 2021. The standardized mean differences with 95% confidence intervals were determined for the main variables, and heterogeneity was analyzed using the I2 test. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Checklist was used. Meta-analysis was performed using the Stata 15.0 software. Among the 2074 records identified, 18 trials were included. The meta-analysis of these trials indicated that virtual reality simulation caused a significant improvement in knowledge with a moderate effect, skill performance with a moderate effect, and satisfaction with a moderate effect compared with the control group. However, virtual reality simulation did not significantly influence self-confidence and self-efficiency. The findings of this study suggested that virtual reality simulation might significantly benefit knowledge, skill performance, and satisfaction but not self-confidence and self-efficiency. Further well-designed randomized controlled trials with a larger sample size are recommended to confirm these findings.