The aim of this study was to estimate the prevalence of migraine in the general Spanish population and its association with socio-demographic and lifestyle factors, self-reported health status, and co-morbidity with other conditions. We analyzed data obtained from adults aged 16 years or older (n = 29,478) who participated in the 2006 Spanish National Health Survey (SNHS), an ongoing, home-based personal interview which examines a nation-wide representative sample of civilian non-institutionalized population residing in main family dwellings (household) of Spain. We analyzed socio-demographic characteristics (gender, age, marital status, educational level, occupational status, and monetary monthly income); self-perceived health status; lifestyle habits (smoking habit, alcohol consumption, sleep habit, physical exercise, and obesity); and presence of other concomitant diseases. The 1-year prevalence of diagnosed migraine (n = 3,433) was 11.02% (95% CI 10.55-11.51). The prevalence was significantly higher among female (15.94%) than male (5.91%) and showed the highest value in the 31-50 years age group (12.11%). Migraine was more common in those of lower income (AOR 1.19, 95% CI 1.01-1.41) and who sleep <8 h/day (AOR 1.18, 95% CI 1.04-1.33). Furthermore, worse health status (AOR 2.04, 95% CI 1.76-2.36) and depression (AOR 1.82 95% CI 1.58-2.11) were related to migraine. Finally, subjects with migraine were significantly more likely to have comorbid conditions, particularly chronic (more than 6 month of duration) neck pain (AOR 2.31, 95% CI 1.98-2.68) and asthma (AOR 1.62, 95% 1.27-2.05). The current Spanish population-based survey has shown that migraine is more frequent in female, between 31 and 50 years and associated to a lower income, poor sleeping, worse health status, depression and several comorbid conditions, particularly chronic neck pain and asthma.