Background: Given the high level of interest and increasing familiarity with virtual reality among adolescents, there is great potential to use virtual reality to address adolescents' unique health care delivery needs while in hospital. While there have been reviews on the use of virtual reality for specific health conditions and procedures, none to date have reviewed the full scope of virtual reality hospital interventions for adolescents who are often combined with children as a homogenous group, despite the fact that adolescents experience virtual environments different from children. Objective: The aim of this review was to systematically identify available evidence regarding the use of virtual reality interventions for adolescent patients in hospital settings to evaluate effectiveness, suitability, and safety and identify opportunities for future research. Methods: PubMed, PsycINFO, Medline, and Scopus databases were searched using keywords and phrases. Retrieved abstracts (n=1525) were double screened, yielding 276 articles for full-text screening. Of these, 8 articles met inclusion criteria. Data were extracted to a standardized coding sheet, and a narrative synthesis was performed due to the heterogeneity of the studies. Results: Four RCTs and 4 single-case reports were identified for inclusion, all of which aimed to reduce pain or anxiety. The scenarios targeted were burn pain, venipuncture, chemotherapy, preoperative anxiety, and palliative care. Three out of 4 RCTs found significant reductions in pain or anxiety outcomes measures when using virtual reality compared to standard care or other distraction techniques; however, only 1 study combined self-reported experiences of pain or anxiety with any physiological measures. Single-case reports relied primarily upon qualitative feedback, with patients reporting reduced pain or anxiety and a preference for virtual reality to no virtual reality. Conclusions: Virtual reality can provide a safe and engaging way to reduce pain and anxiety in adolescents while in hospital, particularly when virtual reality software is highly immersive and specifically designed for therapeutic purposes. As VR becomes more accessible and affordable for use in hospitals, larger and more diverse studies that capitalize on adolescents' interest in and aptitude for virtual reality, and on the full range of capabilities of this emerging technology, are needed to build on these promising results.