BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. METHODS: We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). RESULTS: Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64 in the magnesium sulfate group and 63 in the saline group (OR, 1.0; 95 CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.