Patent foramen ovale (PFO) refers to the gap-like structure left after the septum primum and septum secundum failed to fully fuse, which is closely related to cryptogenic stroke and migraine based on thrombosis and embolism. Gaining a comprehensive understanding of the underlying mechanisms of PFO-associated thrombosis will greatly contribute to the clinical identification of the pathology of PFO and individualized management, benefiting patients fully. This article reviewed the research progress on PFO-related thrombosis mechanisms from paradoxical embolism, in situ thrombosis, left atrial function changes to hypercoagulable state, providing a theoretical basis for the following research on high-risk factors and prevention strategies of PFO-related diseases.