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Patients reporting headache had a significantly higher HIT-6 score than those without (mean 54.47 vs. 38.47, p less then 0.001). The HIT-6 score was significantly higher in patients reporting a migraine compared to those with a tension-type headache (mean 62.13 vs. 46.18, p less then 0.001). In the HADS score and in the SF-12 were not significantly influenced by the occurrence of headache. This study confirms the previously reported frequent occurrence of headache in a large cohort of patients with a confirmed mitochondrial disease.