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BackgroundPrevious studies have shown a connection between physical activity and migraines, but they don’t prove a cause-and-effect relationship due to potential biases in observational methods.MethodsUtilizing accelerometer-measured physical activity data from a cohort of 377,234 participants in the UK Biobank and information from 599,356 European migraine patients (including 48,975 cases and 550,381 controls) obtained from 24 cohorts, we performed a bidirectional Mendelian randomization analysis to investigate the genetic bidirectional causal relationship between accelerometer-measured physical activity and migraines.ResultsResearch findings indicated a slight negative genetic correlation between “average acceleration” physical activity (rg = −0.091, p = 0.011), overall physical activity (rg = −0.081, p = 0.017), and migraine. Nevertheless, no shared genetic components were observed between migraine and “fraction of accelerations > 425 mg” of physical activity (rg = −0.124, p = 0.076). The study results also demonstrated a lack of genetic bidirectional causality between accelerometer-measured physical activity and migraine (“average acceleration”, OR = 1.002, 95% CI 0.975–1.031, p = 0.855, “fraction of accelerations > 425 mg”, OR = 1.127, 95% CI 0.802–1.583, p = 0.488, overall physical activity, OR = 0.961, 95% CI 0.713–1.296, p = 0.799), and vice versa. Additionally, this lack of causal association persists even after adjusting for obesity (OR = 1.005, p = 0.578), education (OR = 1.019, p = 0.143), and depression (OR = 1.005, p = 0.847), either separately or simultaneously.ConclusionThe Mendelian randomization results based on genetic data do not provide support for a causal association between physical activity and migraine.