Objective: Compare adult migraineurs' health related quality of life to adults in the general U.S. population reporting no chronic conditions, and to samples of patients with other chronic conditions. Methods: Subjects (n=845) were surveyed 2–6 months after participation in a placebo-controlled clinical trial and asked to complete a questionnaire including the SF-36 Health Survey, a migraine severity measurement scale and demographics. Results were adjusted for severity of illness and comorbidities. Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions. Results: Response rate was 67%. After adjustment for comorbid conditions, SF-36 scale scores were significantly (P 0.001 ) lower in migraineurs, relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions. Some health dimensions were more affected by migraine than other chronic conditions, while other dimensions were less affected by migraine. Measures of bodily pain, role disability due to physical health and social functioning discriminated best between migraineurs, the U.S. sample, and patients with other chronic conditions. Patients reporting moderate, severe and very severe migraines scored significantly (P £ 0.001 ) lower on five of the eight SF-36 scales than the U.S. sample. Conclusions: Migraine has a unique, significant quality of life burden.