Background and Purpose – We sought to perform a large, prospective, multicenter, blinded study comparing power transcranial color duplex sonography (power TCDS) with intra-arterial digital subtraction angiography (IADSA) in the detection of intracranial aneurysms, Methods-Contemporaneous TCDS and IADSA examinations were performed in 171 subjects with suspected intracranial aneurysm. Via the temporal bone window, a 2-dimensional hand-held noncontrast transcranial duplex ultrasound imaging system was used operating in power and spectral modes. Sonographers were blinded to clinical history and results of brain CT and IADSA. Results – We found that 157 subjects (92%) had an adequate bone window. Sensitivity per patient was 0.78 (95% CI, 0.66 to 0.87) and 0.46 (95% CI, 0.36 to 0.56) for any anterior circulation aneurysms. Sensitivity was 0.35 (95% CT, 0.24 to 0.46) for aneurysms less than or equal to5 mm and 0.81 (95% CI, 0.62 to 0.94) for aneurysms >5 mm, Accuracy was lower for aneurysms on the cavernous and terminal internal carotid arteries, including posterior communicating artery origin (0.71; 95% CI, 0.63 to 0.79), than for those on the anterior (0.82; 95% CI, 0.74 to 0.89) or the middle cerebral arteries (0.79; 95% CI, 0.71 to 0.86). Conclusions-power TCDS is a promising, inexpensive, noninvasive test for anterior circulation intracranial aneurysms but is less sensitive per aneurysm than alternatives such as CT angiography or MR angiography. Sensitivity is poor for aneurysms less than or equal to5 mm in diameter. The internal carotid artery is the most difficult segment to interpret.