Abstract: The foramen ovale is a normal interatrial communication during fetal life that persists after birth in approximately 1/4 adults. The foramen ovale is a potential route for embolic transit from the systemic venous circulation to the brain. In the basal state and peripheral arterial embolism route, patent foramen ovale (PFO) does not cause any clinical symptom. When the pressure of the right atrium transiently or persistently exceeds the pressure of left atrium, righttoleft shunt happens. Emboli or primary thrombus of other body regions is likely to break off, resulting in paradoxical embolism (PDE). PDE has been associated with a series of clinical syndromes including cryptogenic stroke (CS), migraine, systemic hypoxemia from recumbent position breathingorthodeoxia, obstructive sleep apnea syndrome, myocardial infarction with normal coronary, cerebral white matter lesions and arterial gas embolism from neural (cerebral?) decompression illness. However, due to the special anatomy of the aortic arch and brain ischemia, it is more sensitive than other organs. Most PDE assumed transient ischemic attack (TIA) or CS. Although there is convincing circumstantial evidence implicating PFO with CS, the precise role of PFO in the pathogenesis of CS is not still completely understood. This article focuses on the present condition of the study on PDE and CS, especially the results of randomized controlled trials. We expect the above results to propose a new perspective on the treatment of PFO with CS.