To determine the diagnostic performance of transcranial sonography (TCS) in assessing increased echogenic area of the substantia nigra (SN) in patients with Parkinson's disease (PD). Institutional review board approval was obtained for this retrospective study. A total of 278 PD patients (mean age: 64.7 +/- 9.8 y, 100 women) and 300 healthy control patients (mean age: 63.6 +/- 9.3 y, 97 women) were referred for TCS assessment of SN hyper-echogenicity (SN+) from June 2016 to December 2018. Two sonographers independently measured the sizes of the echogenic areas of the SN by TCS imaging in both PD patients and healthy controls. The diagnostic sensitivity, specificity and accuracy of TCS imaging were compared between PD patients and healthy controls. Inter-rater agreement was assessed with the Cohen's K statistic. The sensitivity, specificity and accuracy of readers 1 and 2, respectively, for the identification of SN+ in TCS were 90.3% and 89.6% (251 and 249 of 278), 89.3% and 88.3% (268 and 265 of 300) and 89.8% and 88.9% (519 and 514 of 578). Inter-observer agreement was excellent (K = 0.84). The area under the receiver operating characteristic curve (AUC) for differentiation of PD patients from healthy controls was 0.92 for reader 1 and 0.91 for reader 2. Cutoff values of 0.20 and 0.21 cm(2) were derived from the assessments performed by readers 1 and 2, respectively. We defined 0.20 cm(2) as the optimal cutoff value because it had a higher AUC. TCS is a promising diagnostic technique and can be very helpful in differentiating PD patients from healthy individuals. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.