Transesophageal contrast echocardiography is an effective but semiinvasive technique for the detection of interatrial right-to-left shunts. Transcranial Doppler ultrasound is an alternative noninvasive method, but may be limited by false-positive diagnoses due to intrapulmonary shunting. This study examined the accuracy of transcranial Doppler for the detection of shunt lesions. Transcranial Doppler of the right middle cerebral artery was performed simultaneously with transesophageal and transthoracic contrast echocardiography in 32 patients using agitated saline contrast during normal respiration and Valsalva. Transesophageal contrast echocardiography diagnosed an interatrial right-to-left shunt in 13 patients and intrapulmonary shunting in 6 patients. Transcranial Doppler identified all 13 interatrial right-to-left shunts and an intrapulmonary shunt in 3 of 6 patients. Absence of a shunt was confirmed by transcranial Doppler in 12 of 12 patients. Transcranial Doppler had a sensitivity of 100% (13 of 13), specificity of 100% (18 of 18) and accuracy of 100% (31 of 31) for prediction of an interatrial right-to-left shunt by transesophageal contrast echocardiography. In comparison, transthoracic contrast echocardiography had a sensitivity of 54% (7 of 13), specificity of 94% (17 of 18) and accuracy of 77% (24 of 31). Thus, transcranial Doppler is highly accurate for detection of an interatrial right-to-left shunt and not compromised by physiologic intrapulmonary shunts, whereas transthoracic contrast echocardiography lacks sensitivity. Transcranial Doppler may be useful as an alternative to transesophageal study, where the primary indication for transesophageal echocardiography is exclusion of an interatrial right-to-left shunt.