Objective: To investigate the value of contrast-enhanced transcranial doppler (c-TCD) in the diagnosis of patent foramen ovale (PFO) of patients with migraine and cryptogenic stroke. Methods: A retrospective analysis of 160 patients undergoing c-TCD monitoring in our hospital from June 2014 to June 2019 was performed. Among them, there were 80 cases of patients with migraine (38 cases with aura and 42 cases without aura) in group A, and 80 cases of patients with cryptogenic stroke in group B. The positive detectable rate of PFO in the two groups were calculated and analyzed. Results: The detectable rate was 50.00% in group A, and 40.00% in group B. There was no statistical significance between the two groups (P> 0.05). Among them, the detectable rate of PFO in migraine with aura in group A (62.50%) was higher than that in group B(37.50%). The difference was statistically significant (P<0.05); In the two groups of PFO-positive patients, the difference didn’t have statistical significance, comparing the proportion of the inherent type to that of potential type (P>0.05); There was no statistical significance of the difference between the RLS incidence of grade I and that of grade II among two groups of PFO-positive patients (P>0.05); the incidence of RLS in grade III in group B (50.00%) was higher than that in group A (25.00%), and the difference was statistically significant (P<0.05). Conclusion: c-TCD can accurately screen migraine and cryptogenic stroke caused by PFO, and grade and classify it as a clinical diagnosis of migraine and cryptogenic caused by PFO. It can also act as a objective reference of estimating the effect of treatment in different diseases and preventing cryptogenic stroke.