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The purpose of this pilot study was to determine the effect of virtual reality (VR) on acute pain in pediatric patients with sickle cell disease experiencing vaso-occlusive crisis in one acute-care pediatric emergency department (ED). The randomized sample consisted of 15 participants aged 8 to 17 years admitted to the ED with vaso-occlusive crisis. The control group received standard ED treatment consisting of intravenous (IV) narcotics administered every 30 minutes as needed for up to 3 doses while the intervention group received VR for 15 minutes along with standard treatment. Pain was assessed using the Numerical Rating Scale (NRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) scale. Data were analyzed using an independent samples t test. Counter to hypotheses, results showed pain scores reported by patients using the NRS were not significantly lower when using VR (M=5.71, SD=2.752) than for those who received standard treatment. However, there was a statistically significant difference in the FLACC pain scores (behavioral scale) after 5 minutes of using the VR (p=0.01). Additionally, the average length of stay was shorter for the patients in the intervention group. Although the self-reported pain scores by patients in this sample did not vary significantly when using VR, there was a significant difference in the observed pain scores. This pilot study's data findings support the use of VR with standard treatment in pediatric patients with sickle cell disease who present to the ED in vaso-occlusive crisis. Using multi-modal pain management strategies may decrease length of stay and improve pain scores. Key Words: Virtual reality, sickle cell crisis, pain, children, pediatrics., Sickle cell disease affects approximately 100,000 Americans, and according to global newborn estimates, approximately 300,000 infants are born with sickle cell disease each year (Piel, Steinberg, & Rees, 2017). Vaso-occlusive [...]