Positioning of the patient during the immediate “hyperacute” hours after onset of large artery acute ischemic stroke is an important, yet understudied aspect of nursing care that could impact the course of treatment and clinical outcome in this most severe form of stroke. Since 1968, clinical symptom worsening has been documented in this population when the head of bed (HOB) is elevated to 30o or higher, while clinical improvement or symptom stability has been noted with 0o-HOB positioning. Mechanisms for 0o-HOB clinical improvement include favorable gravitational blood flow conditions and recruitment of collateral blood channels, while in the case of treatment with clot-busting medications, increased blood flow may allow more medication to reach occluded arteries facilitating clot breakdown. Despite this, there remains a divide within the clinical community about what position is best. A recent clinical trial (HeadPoST) failed to answer the question of head positioning for hyperacute large artery stroke patients, enrolling primarily minor, ambulatory strokes with small perforator artery disease that have never been shown to benefit from 0o-HOB positioning, along with intracerebral hemorrhage patients; patients were also enrolled late into symptoms (7 hours) beyond the point where brain tissue salvage is possible. Our team of leading hemodynamic stroke specialists has shown in our pilot work that blood flow can increase as much as 20% on average in large artery stroke territories with 0o-HOB positioning, and that elevated intracranial pressure is absent in the hyperacute phase out to 48 hours from symptom onset. We have also found that pneumonia is rare with 0o-HOB positioning using our extensively piloted methods. We propose a randomized controlled trial of head positioning to determine if 0o-HOB positioning during the early hyperacute phase of large artery ischemic stroke prevents neurological symptom worsening. A novel protocol will be employed that can be executed within current standard of care requirements for rapid thrombectomy treatment with or without clot-busting medications (n=182). Patients will be randomized to one of two groups: 1) 0o-HOB positioning; or, 2) 30o-HOB positioning. We hypothesize that optimal HOB position can be determined by early neurological symptom worsening during the intervention (Aim 1), and propose that real-time deterioration may be a surrogate measure for decreased downstream perfusion, potentially impacting viability of brain at risk for infarction. Aim 2 will confirm that use of 0o-HOB positioning for in large artery ischemic strokes is safe in a larger generalizable population of patients. Use of this nursing measure holds significant promise as an innovative adjunct method to improve ischemic stroke symptoms, and ultimately reduce disability.