Objective Comparative study of value of saline contrast transthoracic echocardiography and transesophageal echocardiography in right-to-left shunt of patent foramen ovale (PFO), and evaluation of 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 transesophageal echocardiography or cardiac catheterization. Both transthoracic echocardiography (cTTE) and 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 right-to-left shunting at the level of the interatrial septum. Results During rest, cTTE detected 135 cases of right to left shunting (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 patients with detected right to left shunting PFO, 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. 59 patients had the same degree of RLS detected in both cTTE and cTEE. Only 17 cases had a lower degree of RLS shunting in cTTE compared to 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. 76 patients had an increase in RLS grade, 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 detection rates of right-to-left shunt degree in patients with patent foramen ovale (PFO-RLS) using contrast transthoracic echocardiography (cTTE) at rest and during Valsalva maneuver showed no significant difference compared to contrast transesophageal echocardiography (cTEE), but the detection of shunt degree was higher with cTEE. However, during cTEE, when patients performed the Valsalva maneuver and the operator applied abdominal pressure by making a fist and relaxing, the right-to-left shunt degree in PFO patients could be significantly increased. Combined with transesophageal echocardiography, it has great value in diagnosing the anatomical structure and morphology of PFO and assessing PFO treatment and closure procedures.