Background and Purpose-Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke. Methods-We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O 2 to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days. Results-Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (Pϭ0.44). 4 and maintenance of blood-brain barrier integrity. 5 HBO has been shown in animal models of both focal and global ischemia to reduce the volume of brain infarction and improve outcome. 6 -8 There have been Ͼ400 cases of ischemic strokes in humans treated with HBO, with more than half of these cases claiming improvement on clinical or experimental grounds. 9 -12 Despite this result, there have been only 2 controlled pilot studies in humans, both using multiple treatments at 1.5-atm pressure absolute (ATA). 13,14 We conducted a pilot study to prospectively assess the efficacy, safety, and feasibility of a 1-time treatment with hyperbaric oxygen at 2.5 ATA in patients with acute ischemic stroke. MethodsThis study was a prospective, sham-controlled, double-blind pilot study comparing HBO with sham in the treatment of ischemic stroke. This study was approved by the Methodist Hospital Institutional Review Board, with patient or proxy consent obtained before enrollment. ParticipantsParticipants included adults Ͼ18 years of age presenting to an emergency department within 24 hours after stroke onset with a measurable deficit on the National Institutes of Health Stroke Scale (NIHSS) and without evidence of hemorrhage on CT scan. Patients waking up with symptoms had time of onset defined as the time they went to sleep. Patients were excluded if they received thrombolytics, had a seizure at onset, had a stroke within 3 months, had improvement on the NIHSS score before treatment, or had an NIHSS score Ͼ22. Patients were also excluded if they had risk factors for HBO, including a history of severe chronic obstructive pulmonary disease, pneumothorax, bowel obstruction, sickle cell disease, or evidence of cardiac arrhythmia deemed by an investigator as potentially mandating emergent intervention. InterventionsSubjects were stratified on the basis of time since symptom onset (0 to 12 or 12 to 24 hours) and subsequently randomized to receive either HBO or sham treatment. The HBO group underwent a 1-time trea...