Background and Purposes Differentiating between acquired stenosis (pathologic) and anatomical slenderness (physiologic) of internal jugular vein (IJV) remain ambiguous. Herein, we aimed to compare the similarities and differences between the two entities. Methods Patients who underwent head and neck computer tomography (CT) and brain magnetic resonance imaging (MRI) were enrolled in this case-control study from January 2016 through October 2021. Results 1487 eligible patients entered final analysis totally. 803 patients had bilateral IJVs imaging without IJV stenosis-related symptoms and presented in three ways: right IJV slenderness (10.5%, n = 85), left IJV slenderness (48.4%, n = 388), and symmetric IJVs (41.1%, n = 330). In patients with asymmetric IJVs, their bilateral jugular foramina were also asymmetric. All involved asymmetric IJVs presented as slenderness without surrounding abnormal collaterals and credible cloudy-like white matter hyper-intensity (WMH). Their cerebral arterial perfusion statuses on brain MR-PWI maps were normal. In contrast, the major patients with IJV stenosis presented with signs and symptoms such as headaches, head noise, etc. In CE-MRV maps, local stenosis of the IJV was surrounded by abnormal venous collaterals in contrast to the lack of abnormal venous collaterals for patients with IJV slenderness. And in CTV maps, the caliber of jugular foramina was mismatched with the transverse diameter of IJV. Moreover, in MRI maps of most of these patients, a cloudy-like WMHs were distributed symmetrically in bilateral periventricular and/or centrum semi vales. These patients also had symmetrical cerebral arterial hypo-perfusion. Seven patients underwent stenting of the IJV stenosis correction, their WMHs attenuated or disappeared subsequently. Conclusions Imaging features in addition to clinical symptoms can be used to differentiate between physiologic IJV slenderness and pathologic IJV stenosis. Notable imagine-defining features for IJV stenosis include local stenosis surrounded by abnormal venous collaterals, cloudy-like WMHs, and mismatch between the transverse diameter of IJV and the caliber of the jugular foramina.