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Background: The COVID-19 pandemic has given rise to more virtual simulation training. This study aimed to review the effectiveness of virtual simulations and their design features in developing clinical reasoning skills among nurses and nursing students., Method: A systematic search in CINAHL, PubMed, Cochrane Library, Embase, ProQuest, PsycINFO, and Scopus was conducted. The PRISMA guidelines, Cochrane's risk of bias, and GRADE was used to assess the articles. Meta-analyses and random-effects meta-regression were performed., Results: The search retrieved 11,105 articles, and 12 randomized controlled trials (RCTs) were included. Meta-analysis demonstrated a significant improvement in clinical reasoning based on applied knowledge and clinical performance among learners in the virtual simulation group compared with the control group. Meta-regression did not identify any significant covariates. Subgroup analyses revealed that virtual simulations with patient management contents, using multiple scenarios with nonimmersive experiences, conducted more than 30-minutes and postscenario feedback were more effective., Conclusions: Virtual simulations can improve clinical reasoning skill. This study may inform nurse educators on how virtual simulation should be designed to optimize the development of clinical reasoning., (© 2022 International Nursing Association for Clinical Simulation and Learning. Published by Elsevier Inc.)