This multicenter, open‐label trial was designed to study the safety of intravenous (IV) sodium valproate in patients with epilepsy. All 318 patients (previously treated with antiepileptic drugs) were hospitalized for seizure control or anticipated seizures. The protocol allowed physicians to set the number of infusions and treatment duration. Adverse events, laboratory studies performed, and seizure activity were documented on case report forms. The patients' mean age was 34.4 years (range, 2–87 years). The most common reason for admission was lack of seizure control (235 patients, 185 of whom were admitted for video‐electroencephalographic monitoring). The median dosage of valproate was 375 mg infused over 1 hour. The median number of doses was four, given over 2 days. In 54 patients (17%), transient adverse events were reported. The most frequent were headache, reaction at the injection site, and nausea (2.2% each); somnolence (1.9%); vomiting (1.6%); and dizziness and taste perversion (1.3% each). No persistent or severe hematologic or serum chemistry abnormalities were found. Vital signs were not significantly affected by the IV infusion of valproate. At the dosages and rates of administration studied, intravenous valproate appears to be safe and well tolerated.