Background: Patent foramen ovale (PFO) is a distinctive aetiology of cryptogenic stroke. The established benchmark for diagnosing PFO is the transoesophageal echocardiography with agitated saline or ‘bubble’ (TOE-b) study. Transcranial Doppler with bubble (TCD-b) or transthoracic echocardiography with bubble (TTE-b) examinations are common initial screening tests for PFO. However, the degree of concordance and discordance between the results of these two approaches remain unclear. Methods: In this prospective observational study, individuals presenting with suspected PFO-associated stroke between 2018 and 2021 underwent simultaneous TCD-b and TTE-b examinations within a joint neuro-cardiovascular laboratory to assess rates of concordance and discordance between TCD-b and TTE-b results. Additionally, data from any subsequent TOE-b studies were gathered. Results: Twenty-two patients were included. Ten patients (45%) exhibited concordantly negative findings and seven patients (32%) had concordantly positive results. Discordant outcomes were recorded in five patients (23%). Subsequently, a subset of seven patients (32%) underwent TOE-b, which confirmed the presence of right-to-left shunts. Among these cases, TCD-b consistently and accurately identified right-to-left shunts in all instances. In contrast, four out of these seven cases exhibited negative TTE-b results. Conclusion: This study indicates that there is significant discordance between TCD-b and TTE-b results (five of 22; 23%). Additionally, the results suggest that TCD-b might be a more effective screening test for detecting PFO compared with TTE-b.