Mindfulness-based interventions that include meditation and mindfulness skills training reduce stress and symptoms of anxiety or depression. However, engaging high-risk youth in interventions is challenging. Virtual reality is a more flexible platform for delivering meditation and may be appealing to youth. Objective: The study objectives were to evaluate the feasibility of delivering virtual reality meditation and of collecting outcome measures, including anxiety and physiologic stress. Methods: A sample of 30 youth experiencing homelessness was enrolled in the study. Youth were randomized to receive 10 minutes of one of three interventions: (1) virtual reality meditation, (2) audio meditation (through a web-based platform), or (3) virtual reality imagery of historical pictures and text. Subjects who consented to the study attended two research visits. The first visit collected survey measures of demographics, mental health, and substance use, and oriented subjects to the intervention platforms. The second visit (1-3 days later) delivered the intervention and collected pre and post outcome measures of anxiety and physiologic stress (salivary cortisol). Changes in anxiety and cortisol at the second visit were compared across groups using a linear regression model in which the primary analysis compared virtual reality meditation to audio meditation and secondary analyses compared virtual reality meditation to virtual reality imagery. Results: Anxiety scores decreased in all groups, with a larger reduction among the virtual reality meditation group (difference=10.8) compared to the web-based meditation or virtual reality images groups (difference=5.8 and 5.0, respectively). After controlling for baseline values, there were no significant group differences in changes in anxiety scores or cortisol levels. In comparing virtual reality meditation and audio meditation, the effect size for anxiety was moderate (Cohen d=0.58) while the effect size for cortisol was small (Cohen d=0.08). Conclusions: Preliminary results suggest that virtual reality meditation has a moderate benefit for anxiety but not physiologic stress. Future research is needed to confirm these results in a larger sample and to investigate whether the effects are sustained or increase with repeated use of virtual reality mediation. Virtual reality meditation appears feasible to deliver among homeless youth and merits further study.