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ObjectivesTo investigate the relationship between right-to-left shunt and migraine to account for the unexplained high prevalence of migraine in patients with epilepsy.DesignThis is a cross-sectional study. The diagnosis and interview process of patients with migraine was based on the International Classification of Headache Disorders-3 beta in patients with epilepsy. Participants underwent transthoracic echocardiography (TTE) with contrast medium to identify right-to-left shunt. The highest number of microbubbles were recorded in the left atrium before the complete microbubble outflow of the right atrium. A moderate-to-large shunt was defined as the presence of 10 or more microbubbles.SettingA single-centre, cross-sectional study in China, 2015–2017.ParticipantsPatients with epilepsy.Primary and secondary outcome measuresThe primary outcome measures were the prevalence of migraine, the prevalence of right-to-left shunt in patients with migraine and those without migraine, and the prevalence of migraine in different degrees of shunting.ResultsThree hundred thirty-nine participants with epilepsy who completed TTE were included in the analysis. The overall prevalence of migraine was 23.0%. One-third of the migraineurs had mild right-to-left shunt and one-fifth of the migraineurs had moderate-to-large right-to-left shunt. Patients with mild shunt did not have a higher prevalence of migraine than those without shunt (26.3% vs 18.1%, p=0.102); however, a higher prevalence of migraine was found in patients with moderate-to-large shunt (39.0% vs 18.1%, OR=2.90, 95% CI=1.41 to 5.98, p=0.003). Patients with migraine and patients without migraine had similar prevalence of mild shunt; however, patients with migraine had more moderate-to-large shunt (20.5% vs 9.6%, p=0.002). Right-to-left shunt and female were factors predicting migraine prevalence.ConclusionsOne-fifth of migraineurs were correlated with moderate-to-large right-to-left shunt which could be an underlying cause of migraine in epilepsy.