Background: Patients with cancer endure numerous procedures over their diagnosis and treatment course, many of which are invasive, causing significant distress beyond the emotional hardship of living with cancer. The utility of virtual reality (VR) as a companion to bone marrow biopsy will be evaluated in terms of its psychological and biological impacts, through patient reported pain scores, anxiety surveys and through assessment of serum biomarkers correlated with pain and anxiety. VR is the immersive simulation of a realistic, three-dimensional environment, generated via interactive software and hardware. The objectives of this study are to determine the feasibility of VR in patients undergoing a bone marrow biopsy and to estimate differences between the two arms in terms of pain and anxiety. In addition, we plan to explore the use of biomarkers associated with stress as a tool to reflect the impact of this intervention. We hypothesize a decrease in pain, anxiety and stress levels peri- and post-procedure in the VR arm compared to the non-VR arm (standard of care). Methods: Patients with hematologic malignancies at USC/Norris Cancer Hospital or Keck Medical Center of USC are being randomized 1:1 to either arm 1 (experimental: VR) or arm 2 (control: no VR). Eight out of 30 planned patients have been enrolled. The VR content is standardized for every subject. It consists of relaxing techniques through visual and auditory input which can last up to one hour. We are using visual analogue scale for both pain (VAS-P) and anxiety (VAS-A) that utilizes numbers and graphic representations between 0 and 10, 0 representing no pain/anxiety at all, to 10 being the worst possible pain/anxiety. Both scales are being measured at 3 defined time points before, during and after the procedure. Usage of pain medications and anesthetics are being recorded for both arms. In addition, we are obtaining baseline levels of the following biomarkers: serum cortisol, highly sensitive C-reactive protein, and fibrinogen. Repeat levels are being collected at specified time intervals to determine if there is a correlation between biomarker levels and perceived pain or anxiety using patient assessed scales. This is a descriptive, feasibility trial that will determine the impact of VR on pain, anxiety, and stress biomarkers during a bone marrow biopsy. Feasibility (i.e. proportion of patients with a successful procedure) will be estimated for each arm separately. The standard error associated difference in success proportions will have a standard error that is less than 0.18. With 30 patients (15 assigned to VR and 15 to standard of care), we will be able to estimate the mean levels of pain and anxiety and biomarkers, as well as changes and differences between the arms with reasonable precision. The implementation of VR in the healthcare setting may serve as a cost-effective, non-pharmacological agent to alleviate pain, anxiety, and stress. Clinical trial information: NCT03568292.