Transient global amnesia is not rare, but its etiology remains unknown. Cerebral ischemia is a suspected cause because high signal intensity is observed on diffusion-weighted brain magnetic resonance imaging; however, previous studies have not established it as a cause. Of the 128 patients (114 females) enrolled in this study, 82 (64.6%) experienced extreme stress before transient global amnesia. The number of female patients with patent foramen ovale was more than that of males. The patent foramen ovale-positive group had fewer vascular risk factors and fewer old ischemic lesions on fluid-attenuated inversion recovery magnetic resonance imaging than the patent foramen ovale-negative group. Brain magnetic resonance imaging confirmed that high signal intensity was more likely to be detected on the initial diffusion-weighted imaging when there was an old lesion detected by fluid-attenuated inversion recovery. Furthermore, a longer period from symptom onset to brain magnetic resonance imaging was associated with a positive initial diffusion-weighted imaging result. It is difficult to attribute one underlying mechanism to all the transient global amnesia cases. This study confirmed that transient global amnesia patients with patent foramen ovale had lesser vascular risk factors and showed fewer old lesions on fluid-attenuated inversion recovery magnetic resonance imaging than those without. These results suggest that transient global amnesia may be caused by a paradoxical embolus rather than ischemia due to traditional vascular risk factors in patients with patent foramen ovale.