Background. To investigate safety and clinical efficacy of percutaneous closure of PFO under TEE guidance in patients with cryptogenic stroke (CS) and migraine, combined PFO and large right-to-left shunt（RLS）. Methods. From January 2018 to June 2021 in our hospital, 128 patients were treated by percutaneous PFO occlusion under TEE guidance in CS and migraine. Effective occlusion rate, complications, cerebral ischemia events, migraine relief, and hospitalization costs were analyzed. Postoperative follow-up were conducted. Results. All the 128 patients were successful in percutaneous PFO occlusion. The average operation time was 20~32 (25.6±4.2) min, the average hospitalization time was 2~3(2.8±0.4) d. There were 122 patients without RLS and 6 patients with medium residual RLS, with the sealing efficiency of 95.31% by TTE and right heart contrast echocardiography. 30 patients with migraine underwent percutaneous PFO occlusion, 24 patients relief after operation, with a relief rate of 80.0%. Postoperative follow-up was conducted for 1-36（28.8±3.6）months, and no follow-up was lost. 98 cases of CS with PFO underwent percutaneous blockade were followed up without cerebral embolism recurrence, 26 of 30 patients with migraine received significant remission of migraine, with remission rate of 86.66%. There were no serious adverse events. Conclusions. For patients with CS and migraine, combined PFO and large RLS, percutaneous PFO occlusion under the guidance of TEE has fewer complications and is safe and effective. It can prevent the recurrence of CS and treat migraine.