A brief migraine-specific quality of life questionnaire was developed to assess the quality of life decrement associated with an acute migraine attack in the 24-hour period following headache onset. The migraine quality of life questionnaire has 15 questions across five domains (work functioning, social functioning, energy, concerns, and symptoms). A prospective, observational study was conducted to evaluate the characteristics of internal consistency, construct and discriminant validity, and responsiveness of the migraine quality of life questionnaire. One hundred thirty-eight subjects with migraine were recruited. One hundred seven subjects completed a baseline and a 24-hour postmigraine quality of life questionnaire, along with a migraine diary for recording headache severity, activity limitation, associated symptoms, duration of headache, and use of migraine medication. All five migraine quality of life questionnaire domains showed good internal consistency (Cronbach's alpha, 0.74-0.95). The strongest correlations were seen between activity limitation and associated symptoms and the migraine quality of life questionnaire work, social, and energy domains. Significant differences in mean questionnaire scores between subjects were found with frequency of medication use, global change in symptoms, headache duration, and severity. All five domains showed significant responses within subjects from a migraine-free period to an acute migraine period (P < 0.0001). In summary, the migraine quality of life questionnaire showed good internal consistency, construct and discriminant validity, and responsiveness to acute migraine attacks.