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Purpose: Needle procedures are among the most distressing aspects of pediatric cancer-related treatment. Virtual reality (VR) distraction offers promise for needle-related pain and distress given its highly immersive and interactive virtual environment. This study assessed the usability (ease of use and understanding, acceptability) of a custom VR intervention for children with cancer undergoing implantable venous access device (IVAD) needle insertion., Method: Three iterative cycles of mixed-method usability testing with semistructured interviews were undertaken to refine the VR., Results: Participants included 17 children and adolescents (8-18 years old) with cancer who used the VR intervention prior to or during IVAD access. Most participants reported the VR as easy to use (82%) and understand (94%), and would like to use it during subsequent needle procedures (94%). Based on usability testing, refinements were made to VR hardware, software, and clinical implementation. Refinements focused on increasing responsiveness, interaction, and immersion of the VR program, reducing head movement for VR interaction, and enabling participant alerts to steps of the procedure by clinical staff. No adverse events of nausea or dizziness were reported., Conclusions: The VR intervention was deemed acceptable and safe. Next steps include assessing feasibility and effectiveness of the VR intervention for pain and distress.