Abstract: AIM To compare contrast transcranial Doppler ultrasonography (c-TCD) and transthoracic contrast echocardiography (c-TTE) for detecting right to left shunt (RLS) in patients with patent foramen ovale (PFO). METHODS The prospective study was conducted in 195 PFO patients who suffered from paradoxical embolism. Both c-TCD and c-TTE were performed for all the patients. Fifty-eight patients with negative results from either c-TCD or c-TTE were further examined by contrast transesophageal echocardiography (c-TEE). The severity of RLS was semi-quantitatively assessed by scaling the numbers of microbubbles (MBs) in the left atrium. Using c-TEE as the reference standard, we analyzed the results of c-TCD and c-TTE. RESULTS c-TTE demonstrated a significantly higher sensitivity for detection of RLS than c-TCD (88.2% vs. 75.9%, P<0.05). The comparison of semi-quantitative grading derived from c-TCD and c-TTE was also significantly different. The positive rate of c-TCD of grade Ⅰ was significantly higher than the positive rate of c-TTE (P<0.01). The positive rate of c-TCD of grade Ⅱ was higher than the positive rate of c-TTE, but with no statistical difference (P>0.05). The positive rates of c-TCD of grade Ⅲ and Ⅳ were both lower than the positive rates of c-TTE (P<0.05). In the 58 patients who were further examined by c-TEE, it was found that the difference in detection rate between c-TCD and c-TEE was significantly different (P<0.01), while the results of c-TTE and c-TEE had a good consistency (P>0.05). CONCLUSION c-TTE is more effective in detection of RLS than c-TCD and can be used as a recommended technique for screening PFO in clinical practice.