Background and purpose: The vertebral artery is made up of four segments, one of which (V3) is connected to highly mobile cervical vertebrae. This connection underlies the common assumption that persons with pre-event histories of mechanical neck movements, such as cervical spine manipulation (cSMT), should experience increased V3 dissection. Methods: Two of the largest case series of vertebral artery dissection describing subjects with and without a specific history of cSMT were reassessed to determine which segment(s) of the vertebral artery was most commonly compromised. Results: The V3 segment was the most commonly involved vertebral artery segment in both the +cSMT group (e.g., V3 vs. V1 prevalence ratio (PR) = 8.46) and the -cSMT group (V3 vs. V1 PR = 4.00). However, V3 vulnerability was augmented by the effect of cSMT. The joint effect of V3 location and exposure to cSMT was greater than if each effect were simply combined. In addition,multiple site lesions were significantly more common than single sites in both the +cSMT group (PR = 2.67, p = 0.008) and the -cSMT group (PR = 2.44, p = 0.0008). Conclusions: In prior studies which identified vertebral artery compromise, those with a history of cSMT were more likely to have involvement of the V3 segment. Although this study does not identify a mechanism which relates vertebral artery dissection and exposure to cSMT, these data are compatible with a greater than additive relation between compromise of an arterial segment thought to be mechanically vulnerable and history of a mechanical event.