Background and Purpose: Recent several studies demonstrated that percutaneous patent foramen ovale (PFO) closure reduced the risk of stroke recurrence for patients with cryptogenic stroke and PFO. Our aim of this retrospective study is to evaluate the usefulness of transcranial color flow imaging (TC-CFI) in the diagnosis of anatomically high risk PFO, in which percutaneous PFO closure is expected to be more effective in preventing embolism. Methods: Subjects were ischemic stroke patients who were investigated the presence of right-to-left shunt (RLS) using TC-CFI and transesophageal echocardiography (TEE). Anatomically high risk PFO evaluated by TEE were defined as satisfying one or more of the following findings: 1) large shunt (more than 20 microbubbles (MB) identified in the left ventricular system), 2) atrial septal aneurism, and 3) the presence of shunt without Valsalva maneuver (VM). TC-CFI was performed in the middle cerebral artery and/or intracranial vertebral artery once without VM and three times with VM, respectively. The number of microembolic signals from MB was determined using international Consensus Criteria (ICC). The accuracy of TC-CFI for high risk PFO diagnosed by TEE was calculated, and then the positive rate of TC-CFI in detecting high risk PFO was also analyzed by TC-CFI’s findings (A: ICC grade II or higher, B: positive without VM, and C: positive on multiple times or in multiple vessels). Results: We analyzed 176 patients (41 females, mean age 64 years) admitted to our facility from July 2019 to July 2021. Of them, 44 patients (25%) had PFO, and 29 patients (16%) were high risk. The diagnostic power of TC-CFI was sufficient, with sensitivity of 93%, specificity of 80%, and accuracy of 89%. The positive rate of each finding was significantly higher in C than in A and B (A: 23%, B: 39%, and C: 55%. P=0.04). Conclusions: To perform the TC-CFI procedure frequently in multiple vessels is useful for screening of high risk PFO.