BACKGROUND AND PURPOSE Flow-induced hemodynamic forces are critical in extra- and intracranial arterial caliber regulation and have been proposed to mediate intracranial aneurysm (IA) formation and rupture. We hypothesized that vascular structural control may be impaired in patients harboring brain aneurysms and sought to examine any differences in extradural internal carotid artery (ICA) caliber profiles. METHODS Ninety-six catheter 2-dimensional angiograms were divided into 3 subgroups: (1) ICA leading to IA (n=38), (2) matched contralateral ICA (n=25), and (3) ICA from nonaneurysmal controls (n=33). ICA diameter was measured proximally beyond the bulb (DProx) and distally at the extradural point of maximal dilation (DMaxDist), yielding maximal distal-to-proximal ratio (RMdp). RESULTS Unlike non-IA controls that tapered smoothly, ICAs leading to IA consistently demonstrated focal sites of abnormal dilation in the distal cervical or petrous extradural segments. RMdp was greater in ICAs leading to IA compared with non-IA controls (1.17±0.1 versus 1.0±0.08; P<0.0001). Matched-pair analysis showed RMdp to be higher in ICAs leading to IA than the corresponding contralateral ICAs (1.19±0.1 versus 1.07±0.11; P=0.001); RMdp from contralateral ICAs was greater than non-IA controls (P=0.005). Among ICAs leading to IA, women showed higher RMdp (1.11±0.12 versus 1.05±0.11; P=0.02) with no relationship to intradural IA location. CONCLUSIONS Measurements of the extradural ICA in patients harboring intradural IA suggest an association with a remote upstream abnormal vascular caliber control consistent with a diffuse flow-mediated structural dysregulation showing laterality and sex dependence.