Objective: The aim of this research was to compare the sensitivity and positive predictive value of contrast transcranial Doppler (c-TCD), contrast- transthoracic echocardiography (c-TTE) and contrast- transesophageal echocardiography (c-TEE), to determine the best method for diagnosing patent foramen ovale (PFO) and to provide a reference for the further improvement of clinical practice. Methods: We investigated 161 patients who suffered from migraines, cryptogenic stroke, TIA, and cerebral infarction of unknown cause. All patients underwent transcatheter examination, and the results of the right heart catheterization (RHC) were considered the gold standard for PFO diagnosis. Results: The present study revealed that c-TTE with the Valsalva maneuver had a higher sensitivity in detecting PFO related right-to-left shunt (PFO-RLS), but it might have a higher rate of misdetection than c-TCD. Conclusion: Patients with suspected PFO can be examined with c-TCD first, and if positive results are obtained, then c-TTE and c-TEE should be performed for further confirmation.