An increased prevalence of intrapulmonary right-to-left shunt (RLS) has been shown in patients with migraine. The aim of this study was to determine whether the size of intrapulmonary RLS was associated with migraine with aura (MA+) and migraine without aura (MA−) in subjects screened for hereditary hemorrhagic telangiectasia. A total of 462 consecutive subjects were screened for hereditary hemorrhagic telangiectasia and underwent transthoracic contrast echocardiography. A pulmonary shunt was established when contrast appeared in the left atrium after 4 cardiac cycles. Shunt size was assessed semiquantitatively as small (<30 microbubbles), moderate (30 to 100 microbubbles), or large (>100 microbubbles). A headache questionnaire was completed by 420 subjects (91%). Two independent neurologists diagnosed migraine according to the International Headache Society criteria. Of 420 screened subjects (mean age 43.4 ± 15.4 years, 61.4% women), 44 (10.5%) had MA+ and 45 (10.7%) had MA−. MA+ was an independent predictor for an intrapulmonary RLS (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.36 to 6.47, p = 0.006) in multivariate analysis. MA− was not correlated with RLS (OR 1.21, 95% CI 0.56 to 2.64, p = 0.60). When comparing patients with MA+ to those without migraine in a multivariate analysis, the presence of an intrapulmonary shunt predicted MA+ (OR 2.5, 95% CI 1.2 to 5.2, p = 0.01), as did female gender (OR 3.15, 95% CI 1.29 to 7.65, p <0.01). The correlation of MA+ and RLS could be entirely attributed to large intrapulmonary shunts (OR 7.61, 95% CI 3.11 to 18.61, p <0.001), as small (OR 0.6, 95% CI 0.13 to 2.78, p = 0.52) and moderate (OR 1.33, 95% CI 0.35 to 5.02, p = 0.68) shunts did not appear to be risk factors for MA+. In conclusion, patients with large intrapulmonary RLS have an increased risk for MA+.