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Background and purpose: Over the last three decades mitochondrial dysfunction has been postulated to be a potential mechanism in migraine pathogenesis. The lifetime prevalence of migraine in persons carrying the 3243A>G mutation in mitochondrial DNA was investigated. Methods: In this cross-sectional study, 57 mDNA 3243A>G mutation carriers between May 2012 and October 2014 were included. As a control group, a population-based cohort from our epidemiological studies on migraine in Danes was used. History of headache and migraine was obtained by telephone interview, based on a validated semi-structured questionnaire, performed by trained physicians. Results: The prevalence of migraine is significantly higher in persons carrying the 3243A>G mutation than in controls (58% vs. 18%; P < 0.001). This applies for both subforms of migraine, migraine without aura (47% vs. 12%; P < 0.001) and migraine with aura (18% vs. 6%; P < 0.001), and in females (58% vs. 24%; P < 0.001) and males (58% vs. 12%; P < 0.001) for any migraine. Conclusions: A high prevalence of migraine in persons with the mDNA 3243A>G mutation was found. This finding suggests a clinical association between a monogenetically inherited disorder of mitochondrial dysfunction and susceptibility to migraine. Mitochondrial DNA aberrations may contribute to the pathogenesis of migraine. [ABSTRACT FROM AUTHOR]