A small magnetic resonance imaging (MRI) study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. With 1.5-T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n = 138) and controls (n = 75), with multivariate regression analysis. Analyses were conducted in age strata (< 50, n = 112; > or = 50) because iron measures are increasingly influenced by non-iron-related factors in the older group. Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared with controls, T2 values were lower in the putamen (P = 0.02), globus pallidus (P = 0.03) and red nucleus (P = 0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine history had lower T2 values in the putamen (P = 0.01), caudate (P = 0.04) and red nucleus (P = 0.001). Repeated migraine attacks are associated with increased iron concentration/accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache.