Objective: To analyze the contrast transesophageal echocardiography,c-TEE (c-TEE) characteristics in patients with migraine and cryptogenic stroke and to explore the role of c-TEE in the assessment of different disease right-to-left shunt types. Methods: One hundred and forty-six patients with migraine associated with suspected right-to-left shunt and 167 patients with cryptogenic stroke admitted to our hospital from January 2018 to October 2018 were selected for retrospective analysis. All enrolled patients completed TEE and c-TEE examinations, analyzed the general conditions of patients, and compared the positive results of right-to-left shunt and the characteristics of the source and degree of shunt of microbubbles in the left atrium between the two groups with different examination methods. Results: The migraine group was predominantly female and younger than patients with cryptogenic stroke (all P < 0.05). There were 66 cases of pulmonary-related right-to-left shunts in the migraine group and 71 cases in the cryptogenic stroke group. There was no statistical difference in the proportion of different types of right-to-left shunts between the two groups. 82 cases of PFO were observed in the cryptogenic stroke group and 32 cases in the migraine group by TEE, and no pulmonary vein abnormalities were found in either group. 80 cases of PFO-RLS were observed in the migraine group and 96 cases in the cryptogenic stroke group by c-TEE; there was no statistically significant difference in the detection rate of PFO between TEE and c-TEE in the cryptogenic stroke group. In the migraine group, the c-TEE PFO detection rate was significantly higher than that of TEE (P < 0.05). c-TEE showed that the grade 1 RLS in the migraine group (65/12751%) was significantly higher than that in the cryptogenic stroke group (38/153, 25%), in which both P-RLS and PFO-RLS were significantly higher in the migraine patients than in the cryptogenic stroke patients (both P < 0.05 ); grade 3 RLS in the cryptogenic stroke group (51/153, 33%) was significantly higher than grade 3 RLS in the migraine group (22/127, 18%) (P < 0.05), with PFO-RLS significantly higher in the cryptogenic stroke group than in the migraine group, but the difference in P-RLS between the two groups was not statistically significant. Conclusion: The study initially verified that c-TEE can clarify the source of right-to-left shunt in migraine and cryptogenic stroke patients and perform semi-quantitative analysis to provide a basis for possible etiologic diagnosis.