Objective:This study aims to compare transthoracic echocardiography(TTE)and transesophageal echocardiography (TEE)combined with contrast echocardiography in the evaluation of right -to -left shunt(RLS)of patent foramen ovale(PFO),and propose the optimal diagnostic strategy. Methods:A retrospective study was conducted on 186 patients admitted the cardiovascular department of the First Affiliated Hospital of Nanjing Medical University from February 2020 to February 2022 with cryptogenic stroke (CS),transient ischemic attack(TIA)and migraine who were confirmed to have a patent foramen ovale(PFO)through TEE or cardiac catheterization. Both contrast transthoracic echocardiography(cTTE)and contrast transesophageal echocardiography(cTEE)were performed. In addition,during cTEE,the operator clenched their fist and placed it on the patient’s abdomen,applying pressure and then releasing it,while the patient performed a Valsalva maneuver. The number of microbubbles appearing in the left atrium and left ventricle within three cardiac cycles was observed to assess the degree of RLS at the level of the interatrial septum. Results:During rest,cTTE detected 136 cases of RLS,while cTEE detected 140 cases of RLS. During the Valsalva maneuver,cTTE detected 186 cases of RLS,and cTEE also detected 186 cases of RLS,indicating a significant increase in the detection rate of PFO-RLS during the Valsalva maneuver compared to the rest state,regardless of the cTTE or cTEE method. Among the PFO patients with RLS detected, cTTE classified 27 cases as grade Ⅰ,31 cases as grade Ⅱ,and 128 cases as grade Ⅲ. On the other hand,cTEE classified 80 cases as grade I,56 cases as grade Ⅱ,and 50 cases as grade Ⅲ. Among these cases,110 patients had a higher RLS degree in cTTE compared to cTEE,with 46 cases being grade Ⅲ in cTTE and grade Ⅱ in cTEE,43 cases being grade Ⅲ in cTTE and grade Ⅰ in cTEE,and 21 cases being grade Ⅱ in cTTE and grade Ⅰ in cTEE. During the Valsalva maneuver with cTEE,while the operator clenched their fist and applied pressure on the patient’s abdomen and then released it,35 cases were classified as grade Ⅰ,46 cases as grade Ⅱ,and 105 cases as grade Ⅲ. There were 76 patients with an increase in RLS degree,including 21 patients who upgraded from grade Ⅰ to grade Ⅱ,24 patients who upgraded from grade Ⅰ to grade Ⅲ,and 31 patients who upgraded from grade Ⅱ to grade Ⅲ. The proportion of patients with moderate to large shunting significantly increased. Conclusion:The RLS level detected by cTTE is higher than that of cTEE. During the cTEE examination,when the patient cooperates with the examiner to press,the degree of RLS detected under Valsalva’s action increases. The combination of cTTE and TEE in diagnosing the anatomical structure and morphology of PFO is of great value for the treatment and preoperative evaluation of PFO occlusion.