: This multicenter study investigated the safety and efficacy of intravenous valproate in acute migraine attacks and the possible impact of prophylactic valproate pre-treatment. Thirty-six patients established on migraine prophylaxis were administered 500 mg sodium valproate intravenously against acute migraine attacks. Pain development was assessed by visual analogue scale up to a 24 hours follow up interview to detect e.g. possible relapse symptoms. A subgroup analysis examined whether prophylactic treatment with valproate affected its acute anti-migraine efficacy. A meaningful headache reduction within two hours was achieved in all 12 patients with and in 20 out of 24 patients without valproate prophylaxis. Headache-associated signs and symptoms were substantially reduced. No serious side-effects were reported. The results confirm the therapeutic value of intravenous valproate in acute migraine attacks described in literature and show a beneficial effect on all investigated efficacy parameters with a trend to even better response in patients receiving valproate prophylaxis.