Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30–60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in >50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.