OBJECTIVES: To compare comorbid conditions and economic and humanistic factors between migraine sufferers and non-sufferers using data from the 2005 U.S. National Health and Wellness Survey (NHWS). METHODS: Cases were defined as those respondents reporting physician diagnosis of migraine. Propensity score matching methods were used to identify an identical number of respondents not experiencing migraine (controls) from the NHWS population matched for age, gender, and race. Cases and controls were compared for rates of comorbid conditions and lifestyle factors, economic parameters such as resource utilization and work productivity (WPAI), and quality of life (SF-8). Statistical analyses included chi-square tests and t-tests. RESULTS: Of the 39,141 NHWS respondents, 4,337 (11.1%) reported a physician diagnosis of migraine and were matched to 4,337 controls. Approximately 79.6% of cases and controls were female, 88.0% were white, and the mean age was 42 (SD=12.5). Migraine sufferers reported higher rates of lifetime cases of arthritis (32.7% vs. 20.6%; p<0.001) and gastroesophageal reflux disease (23.3% vs. 11.9%; p<0.001), and higher rates of depression in the past year (43.7% vs. 25.7%; p<0.001) than their matched controls, as well as higher rates of hypercholesterolemia and hypertension (both p<0.001). Migraine sufferers had higher rates of emergency rooms visits (22.8% vs. 12.9%; p<0.001) and hospitalizations (11.9% vs. 7.5%; p<0.001) in the past six months, reported lower scores on both physical (44.8 vs. 49.2; p<0.001) and mental (44.5 vs. 48.3; p<0.001) components of the SF-8, and had greater overall work impairment due to health (20.6% vs. 12.1%; p<0.001) than their non-migraine counterparts. CONCLUSION: Migraineurs have higher proportions of comorbid conditions, use more healthcare resources, miss more time from work, and experience worse health-related quality of life than non-migraine sufferers. These results highlight the importance of providing adequate care for these patients, to treat not only migraines, but also comorbid conditions.