Abstract: AIM To screen the relevance ratio of patent foramen ovale (PFO) in patients with cryptogenic stroke, unexplained syncope, and migraine utilizing transthoracic-echocardiography (TTE) and contrast transthoracic-echocardiography (cTTE) and to observe the midterm outcomes of percutaneous closure of PFO. METHODS One hundred and sixty-seven patients diagnosed with cryptogenic stroke, unexplained syncope, and migraine were examined by TTE and cTTE. The patients were quantified as Grade I, Grade Ⅱ and Grade Ⅲ, according to degree of the right-to-left shunt (RLS). Twenty-two Grade Ⅲ patients were verified by right ventricular echocardiography as having PFO and proper occluders were chosen for closure. These patients were followed up in 1, 3 and 6 months after operation and they were reexamined by cTTE 6 months post-operation. RESULTS Among the 167 patients who were examined by cTTE, 67 patients (40.1%) had RLS in the resting state and 85 patients (50.9%) had RLS after Valsalva maneuver. Among the 85 patients, 23 patients (13.8%) were Grade I, 12 patients (7.2%) Grade Ⅱ and 50 patients (29.9%) Grade Ⅲ. The detection rate for the combination of cryptogenic stroke and PFO was 43.5%, for the combination of unexplained syncope and PFO the detection rate was 68.0%, and for the combination of migraine and PFO the detection rate was 47.9%. Six-month following-up after closure operation revealed that clinical symptoms improved in the 22 patients and no complications were found. TTE reexamination showed no residual shunt. CONCLUSION The combination of TTE and cTTE is an important noninvasive examination for screening PFO. Their combination has a high detection rate for cryptogenic stroke, unexplained syncope, and migraine. Percutaneous closure of PFO can effectively prevent recurrence of cryptogenic stroke and syncope and markedly reduce the symptoms of migraine.