BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography (TCCD) is a diagnostic technique for evaluation of intracranial arteries in patients with acute stroke. Echo-enhancing contrast agents (EEAs) are necessary to visualize intracranial vessels in up to 30% of patients because of limited acoustic bone windows. In this study, we assessed the diagnostic efficacy of echo-enhanced TCCD (eTCCD) in correlation with the gold standard, digital subtraction angiography (DSA). METHODS: We prospectively evaluated all patients with eTCCD who subsequently underwent DSA for evaluation of cerebrovascular symptoms over a 24-month period. We administered Levovist as an EEA. Two blinded reviewers analyzed all eTCCD findings and correlated them with DSA. RESULTS: We included 132 consecutive patients (40 women, 92 men; mean age, 58 ± 14 years) with 164 datasets: 24/164 had normal findings, 98/164 had abnormalities of extracranial carotid arteries, 32/164 had abnormalities of intracranial arteries, and 21/164 had abnormalities in vertebrobasilar circulation as determined by DSA. For eTCCD, we found a sensitivity of 82% (95% confidence interval [CI]: 75%-90%), a specificity of 98% (95% CI: 90%-100%), a positive predictive value of 99% (95% CI: 94%-100%), and a negative predictive value of 75% (95% CI: 64%-85%); 7/164 (4%) examinations were inconclusive because of insufficient bone windows. The interobserver agreement was almost perfect (κ value, 0.92 95% CI: 0.87-0.97). CONCLUSION: eTCCD provides high diagnostic validity for the status of the major intracranial arteries. In particular, a normal vessel status reliably assessed by an experienced sonographer could supersede further imaging procedures. In patients with acute ischemic stroke not eligible for established angiographic techniques, eTCCD may be useful as an alternative imaging technique.