Moyamoya syndrome in a sickle cell disease patient may be a difficult task to manage in the setting of a vaso-occlusive pain crisis. Maintaining stable blood pressure is necessary to prevent stroke as both hypertension and hypotension can be detrimental to the patient, leading to hemorrhagic and ischemic stroke, respectively. Opioid management for pain control in such patients must be taken into consideration. Because every patient is unique, opioid regimens should be optimized to relieve patients’ specific pain while also practicing non-maleficence in preventing hypotension and strokes.