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Contrast-enhanced transesophageal echocardiography (c-TEE) is considered the gold standard for the diagnosis of patent foramen ovale. The purpose of this study was to compare the practical use of contrast-enhanced transcranial color Doppler (c-TCD) to define its role in the diagnostic pathway of patent foramen ovale.Two hundred and eighty-six consecutive patients with a presumed paradoxical cerebrovascular event were investigated by both c-TEE and c-TCD for the detection of patent foramen ovale. Considering c-TEE as the gold standard for statistical comparison, the sensitivity, specificity, positive predictive value, negative predictive value and global diagnostic accuracy of c-TCD were assessed.Among the entire cohort of patients (286), 156 (54%) showed positive and 116 (41%) negative findings with both the examinations; 10 patients (3%) had a negative result with c-TCD and a positive one with c-TEE; four (1%) had a positive result with c-TCD and a negative one with c-TEE. Thus, for c-TCD, we defined a sensitivity of 94% (95% confidence limits 90–98) and a specificity of 97% (94–100). The positive predictive value for the detection of the shunt was 98% (95% confidence limit 96–100) and the negative predictive value was 92% (95% confidence limit 87–97). Global diagnostic accuracy was 95% (95% confidence limit 92–98). The two examinations showed a strong statistical correlation (r = 0.90; R2 = 0.81; P < 0.001).c-TDC results in an effective, safe and low cost examination, with excellent sensitivity and specificity as compared with c-TEE.