Background <p>Although pharmacological and non-pharmacological therapy are available, pain management in the emergency department (ED) may be difficult. In recent years, virtual reality (VR) has emerged as a practical distraction approach for pain relief, especially in children and adolescents. However, little is known about the efficacy of VR in the ED. Therefore, the current study investigated the effect of VR on pain management in adult and pediatric patients in the ED.</p> Objectives <p>Primary objective: To assess the effect of VR on pain intensity. Secondary objectives: To investigate patient satisfaction with VR as a pain management method and to assess the incidence of cybersickness after VR intervention.</p> Search methods <p>We comprehensively searched CENTRAL, Google Scholar, PubMed, and MEDLINE databases for all studies published until May 2024. The search was limited to records authored in English and it did not include grey literature, such as theses and dissertations.</p> Selection criteria <p>We included randomized and non-randomized studies reporting the use of VR to manage pain in patients presenting to the ED.</p> Results <p>The pooled analysis demonstrated a significant reduction in pain scores with the use of VR (SMD: -0.67; <i>p</i> = 0.001). Furthermore, subgroup analyses showed consistent pain reduction with the use of VR across adult and pediatric patients (SMD: -1.08; <i>p</i> = 0.01 and SMD: -0.39; <i>p</i> = 0.009, respectively). Significant pain reduction was also observed in patients undergoing minor medical procedures and those with acute pain unrelated to medical procedures (SMD: -1.55; <i>p</i> = 0.03 and SMD: -0.32; <i>p</i> = 0.002, respectively).</p> Conclusion <p>Overall, VR offers effective pain management in adults and pediatric patients with non-procedural acute pain and those undergoing painful procedures in the ED.</p> Systemic review protocol registration <p>PROSPERO: CRD42024609121.</p> Clinical trial number <p>Not applicable.</p>