CONTEXT: Sickle cell disease (SCD) vaso-occlusive crisis (VOC) remains an important cause of acute pain in pediatrics and the most common SCD complication. Pain management recommendations in SCD include nonpharmacological interventions. Yoga is one nonpharmacological intervention that has been shown to reduce pain in some populations; however, evidence is lacking in children with VOC.OBJECTIVES: The primary objective of this study was to compare the effect of yoga vs. an attention control on pain in children with VOC. The secondary objectives were to compare the effect of yoga vs. an attention control on anxiety, lengths of stay, and opioid use in this population. METHODS: Patients were eligible if they had a diagnosis of SCD, were 5-21 years old, were hospitalized for uncomplicated VOC, and had an admission pain score of ≥7. Subjects were stratified based on disease severity and randomized to the yoga or control group. RESULTS: Eighty-three percent of patients approached (N = 73) enrolled on study. There were no significant differences in baseline clinical or demographic factors between groups. Compared with the control group, children randomized to yoga had a significantly greater reduction in mean pain score after one yoga session (-0.6 ± 0.96 vs. 0.0 ± 1.37; P = 0.029). There were no significant differences in anxiety, lengths of stay, or opioid use between the two groups. CONCLUSION: This study provides evidence that yoga is an acceptable, feasible, and helpful intervention for hospitalized children with VOC. Future research should further examine yoga for children with SCD pain in the inpatient and outpatient settings.