The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence.