Objective.- To prospectively evaluate the efficacy of perimenstrual prophylaxis with eletriptan to reduce headaches in women identified with menstrual migraine (MM). Methods.- Female migraineurs self-reporting a substantial relationship between migraine and menses were evaluated with 3 consecutive months of daily headache recording diaries. A relationship between menses and migraine was evaluated using International Classification of Headache Disorders (ICHD-II) criteria and a probability model called Probability MM. Women prospectively diagnosed with ICHD-II MM were treated for 3 consecutive months with perimenstrual eletriptan 20 mg 3 times daily starting 2 days prior to the expected onset of menstruation and continued for a total of 6 days. Headache activity was compared during the 3 months of recording prior to eletriptan therapy and 3 months with eletriptan perimenstrual prevention therapy. Results.- Three months of pretreatment prospective diaries were completed by 126 women. ICHD-II menstrually related migraine was diagnosed in 74%, with pure MM in 7%. Among those women diagnosed with ICHD-II MM, 61 completed at least 1 treatment month. Overall change in headache activity was a 46% decrease. The mean percentage of treated menses without migraine occurring during the 6 days of treatment was 71%. The percentage of subjects with 1, 2, and 3 migraine-free menstrual periods (no migraines occurring 2 days before menses through the first 3 days of menstruation) with eletriptan, respectively, were 14%, 19%, and 53%. Among those subjects who remained headache-free during the 6 days of eletriptan treatment, migraine occurred during the 3 days immediately after discontinuing eletriptan for 9%. Perimenstrual eletriptan was generally tolerated and no abnormalities were identified on the 6th day of treatment using either blood pressure recording or electrocardiogram. Conclusions.- Among patients with prospectively identified MM, eletriptan 20 mg 3 times daily effectively reduced MM. A significant reduction in headache activity occurred for 53% of patients.