Transthoracic Doppler echocardiography (TDE) has been described as a feasible and accurate technique to noninvasively assess coronary flow reserve (CFR) in the left anterior descending artery (LAD). This study was designed to evaluate whether serial assessment of CFR in the LAD using TDE allows detection of restenosis after previously performed angioplasty. Thirty-three consecutive patients with single-vessel coronary artery disease of the LAD scheduled for angioplasty underwent assessment of coronary flow velocity at rest and during adenosine-induced hyperemia in the distal LAD using high-frequency TDE. CFR was calculated as the ratio of hyperemic to basal systolic/diastolic mean velocity. Investigations were performed before and immediately after angioplasty, and at the time of control angiography after 3 months. CFR results by TDE were compared with intracoronary Doppler guide wire measurements. Adequate pulse-wave Doppler signals to measure CFR were obtained in 30 patients (91%) using TDE. There was close correlation between echocardiographically and intracoronary derived CFR results (r = 0.80, 0.79, and 0.87 before angioplasty, early after, and at 3- month control angiography, respectively; p <0.001). Using a cut-off value of CFR < or =2.0 to identify significant coronary artery disease, TDE detected LAD restenosis with a sensitivity of 89% and specificity of 90%. Thus, high-frequency TDE is a feasible technique to noninvasively assess CFR in the LAD with results closely corresponding to invasive measurements. Defining a cut-off value of CFR < or =2.0, the technique has the potential to reliably detect LAD stenosis after coronary intervention.