Background: Increased blood pressure variability (BPV) has been associated with worse outcomes in acute stroke. The effect of hyperacute (<4 hours) BPV on early neurologic deterioration (END) has not been described. Objective: To investigate whether BPV in the first hours after stroke onset is associated with END from prehospital evaluation to presentation at the emergency department Methods: All patients enrolled in the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 trial were included. FAST-MAG was a multicenter, randomized, double-blind, placebo-controlled study looking at whether initiation of magnesium sulfate (20 grams/24 hours) in the prehospital setting of acute stroke would reduce disability. Study agent was initiated prior to hospital arrival < 2 hours from symptom onset. BPV was defined as the standard deviation of systolic blood pressure of all readings obtained by 4 hours after initiation of study agent. END was diagnosed as Glasgow Coma Scale (GCS) decrease by ≥ 2 points between the prehospital evaluation and post-emergency department arrival assessment by a study nurse. Results: There were 1,700 cases evaluated by paramedics 24 minutes (15-45 IQR), and by study nurses 150 minutes (120-180) after symptom onset with a median of 6 (IQR 5-6) BP readings. The mean (±SD) age was 69±13 years, 42.6% were women, and the median prehospital GCS was 15 (IQR 14-15). The final diagnosis was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. END was seen in 202 (12%) of subjects, with higher rates noted in those with intracerebral hemorrhage (ICH) compared to cerebral ischemia (31% vs 6%). Overall, there was greater BPV in patients with END (23mmHg vs 15mmHg, p<0.001). Blood pressure variability was greater in cases of cerebral ischemia with END (N=1,245, 18mmHg vs 15mmHg, p=0.004) and in ICH cases with END (N=387, 23mmHg vs 15mmHg, p<0.001). Conclusion: Greater blood pressure variability is associated with early neurologic deterioration in patients with cerebral ischemia and ICH evaluated <2 hours from symptom onset.