Substantia nigra (SN) hyperechogenicity measured by transcranial sonography (TCS) is a promising biomarker for Parkinson disease (PD). The aim of this study was to explore the diagnostic accuracy of SN hyperechogenicity (SN) for differentiating PD from essential tremor (ET). A total of 119 patients with PD, 106 ET patients and 112 healthy controls that underwent TCS from November 2016 to February 2019 were included in this single-center retrospective case-control study. Two reviewers who were blinded to clinical information independently measured the SN by TCS imaging. The diagnostic sensitivity, specificity, and accuracy of TCS imaging were evaluated between the PD and healthy controls and between patients with PD and ET. Interrater agreement was assessed with the Cohen κ statistic. TCS imaging of the SN allowed to differentiate between patients with PD and ET with a sensitivity (91.6% and 90.8%) and specificity (91.5% and 89.6%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.87). In addition, measurement of the SN allowed to differentiate between patients with PD and healthy subjects with a sensitivity (91.6% and 90.8%) and specificity (88.4% and 89.3%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.91). Measurement of SN on TCS images could be a useful tool to distinguishing patients with PD from those with ET.