Since the concept of paradoxical embolism was introduced by Cohnheim in 1877 through the autopsy of a young woman who died of stroke with a combined patent foramen ovale, the relationship between patent foramen ovale and embolism of the body circulation has not received sufficient attention from us for a century and has only recently attracted the attention of the academic community. The foramen ovale is a physiologic channel during fetal life that allows umbilical venous blood to flow from the right atrium into the left atrium to maintain fetal circulation. The foramen ovale is completely closed in 18% of children at 1 year of age and 50% of children at 2 years of age; if the foramen ovale does not close after 3 years of age, it is called patent foramen ovale (PFO). The detection rate is 20-30% in the population. It was previously thought that there was no clear pathological significance of patent foramen ovale, but recent studies have shown that patent foramen ovale may be associated with certain clinical conditions, such as cerebral embolism due to paradoxical embolism. Cerebral embolism is one of the important manifestations of heart disease. The most common direct causes are chronic atrial fibrillation; shedding of inflammatory redundancies on the valves in infective endocarditis; appendage thrombi from myocardial infarction or cardiomyopathy; and cardiac mucinous tumors are also frequently caused. However, paradoxical embolism caused by an embolus from the venous system passing through an unclosed foramen ovale is often overlooked. Paradoxical embolism refers to the arrival of an embolus from the venous system or the right heart through an abnormal intracardiac (patent foramen ovale, atrial septal defect, etc.) or extracardiac (pulmonary arteriovenous fistula, etc.) channel to the left heart, causing embolism in the circulation. Normally, the pressure in the left heart system is higher than that in the right heart system, and the patent foramen ovale does not cause a right-to-left shunt. However, in some cases such as cough, pulmonary embolism, or defecation, increased pressure in the right heart can cause a right-to-left shunt through the patent foramen ovale and cause a paradoxical embolism. The cause of stroke is unknown in about 25-40% of stroke patients, i.e. “cryptogenic stroke”. Studies have shown that the detection rate of patent foramen ovale is higher in patients with cryptogenic stroke than in the general population, thus raising concerns about the relationship between patent foramen ovale and embolism in the body circulation. In addition to cerebral embolism, several other clinical conditions may be associated with patent foramen ovale, such as myocardial infarction, peripheral artery embolism, decompression sickness, plateau pulmonary edema, migraine, exercise-induced hypoxemia and upright hypoxemia, and sleep apnea syndrome. The diagnosis of patent foramen ovale is based on the presence of manifestations of embolism in the body circulation, especially if there is no other explanation for the embolism, combined with TCD foaming test and echocardiographic (transthoracic and transesophageal) right heart sonography, which usually requires valsalva’s maneuver or increased intrathoracic pressure such as coughing to determine the presence of a right-to-left shunt. There is still no unified understanding of the treatment of patent foramen ovale. Asymptomatic patent foramen ovale does not require treatment. In addition to antiplatelet or anticoagulation therapy, transcatheter foramen ovale closure is a treatment option to be considered for clinical disease caused by foramen ovale noncompaction. It is mainly used for secondary prevention of the following diseases, including cerebral infarction due to paradoxical embolism, myocardial infarction, peripheral arterial embolism, plateau pulmonary edema, and decompression sickness. Closure of the foramen ovale may be therapeutic for some diseases, such as migraine, upright hypoxia, and exercise-induced hypoxia. There are also pathophysiologic conditions that require closure of the foramen ovale as primary prevention of paradoxical embolism, such as when pulmonary embolism and carcinoid tumors occur. However, many clinical questions remain to be addressed, such as what is the exact role of patent foramen ovale in the pathogenesis of embolism in patients, and which types of patent foramen ovale are more prone to embolism? What is the sensitivity of the different detection methods and whether transcatheter closure of the foramen ovale can indeed reduce stroke recurrence? In clinical practice, it is important to pay attention to the relationship between unclosed foramen ovale and paradoxical embolism, but also not to “take everything for granted” and close the foramen ovale without evaluation. For example, we have a patient whose symptoms of cerebrovascular disease all occurred during coughing, and TCD foam test and TEE right heart angiography both indicated that the foramen ovale was not closed without other cerebrovascular causes, so the patient was closed the foramen ovale by catheter, and then the patient had no more symptoms, indicating the importance of clinical evaluation. Regarding whether transcatheter closure of the foramen ovale reduces embolism in the body circulation, the results of different clinical trials have varied, with both positive and negative results, suggesting that we do need to clinically screen appropriate patients for unclosed foramen ovale closure and individualize the treatment in specific clinical practice, and also look forward to further clinical trial evidence.