The efficacy of hyperbaric oxygen (HBO) therapy combined with intravenous edaravone (free radical scavenger) administration was prospectively investigated in patients with acute embolic stroke involving the anterior cerebral circulation. Patients with acute embolic stroke in the anterior cerebral circulation admitted within 48 hours of onset from August 2001 to March 2002 with National Institutes of Health Stroke Scale (NIHSS) scores on admission of 5 or more were assigned randomly to HBO and control groups. The HBO group underwent HBO therapy combined with intravenous edaravone administration for 7 days, whereas the control group received only conventional treatment. The primary endpoint was the modified Rankin Scale score at 90 days (favorable outcome, score 0 or 1). The secondary endpoint was the NIHSS score at 7 days. Analysis was carried out by intention to treat. Six of the 19 patients in the HBO group, but only one of the 19 patients in the control group, had favorable outcomes at 90 days (p < 0.05), although NIHSS score at 7 days did not differ significantly between the two groups. HBO therapy combined with intravenous edaravone administration appears to be effective for the treatment of patients with acute embolic stroke in the anterior cerebral circulation.