To evaluate the clinical efficacy and safety of patent foramen ovale (PFO) transcatheter closure treatment on patients who have migraine with right-to-left shunt (RLS). Methods: One hundred and fourteen patients with migraine combined with RLS were randomized into operation group (to undergo PFO transcatheter closure, n=57) or control group (to receive conventional medical therapy, n=57). The headache-impact-test score (HIT-6) and the reduction to baseline in HIT-6 at one year after treatment were compared between 2 groups. The incidence rates of complications at one month and one year after treatment, the residual RLS at 24 h and one year after treatment, and the new onset of cerebral infarction at one year after treatment were compared. Results: One year after treatment, the HIT-6 grade was (49.57 ± 4.58) and the difference value was (14.38±3.57) in the operated group, and the values were (56.85±5.69) and (8.64±2.24) in the control group respectively (P<0.05). There were 11 (19.30%) patients with complications which disappeared after one year of operation. There were 8 (14.04% ) patients with large residual shunt at 24 h while only 1 (1.92%) patient with large residual shunt after one year of operation. Seven in operation group and 17 in control group developed new cerebral infarction after one year (P<0.05). Conclusion: PFO closure is a safe and effective way to treat patients who have migraine with RLS. It can also reduce the risk of stroke