Spectral-domain Optical Coherence Tomography (SD-OCT) is a non-invasive modality for acquiring high reso- lution, three-dimensional (3D) cross sectional volumetric images of the retina and the subretinal layers. SD-OCT also allows the detailed imaging of retinal pathology, aiding clinicians in the diagnosis of sight degrading diseases such as age-related macular degeneration (AMD) and glaucoma.1 Disease diagnosis, assessment, and treatment requires a patient to undergo multiple OCT scans, possibly using different scanning devices, to accurately and precisely gauge disease activity, progression and treatment success. However, the use of OCT imaging devices from different vendors, combined with patient movement may result in poor scan spatial correlation, potentially leading to incorrect patient diagnosis or treatment analysis. Image registration can be used to precisely compare disease states by registering differing 3D scans to one another. In order to align 3D scans from different time- points and vendors using registration, landmarks are required, the most obvious being the retinal vasculature. Presented here is a fully automated cross-vendor method to acquire retina vessel locations for OCT registration from fovea centred 3D SD-OCT scans based on vessel shadows. Noise filtered OCT scans are flattened based on vendor retinal layer segmentation, to extract the retinal pigment epithelium (RPE) layer of the retina. Voxel based layer profile analysis and k-means clustering is used to extract candidate vessel shadow regions from the RPE layer. In conjunction, the extracted RPE layers are combined to generate a projection image featuring all candidate vessel shadows. Image processing methods for vessel segmentation of the OCT constructed projection image are then applied to optimize the accuracy of OCT vessel shadow segmentation through the removal of false positive shadow regions such as those caused by exudates and cysts. Validation of segmented vessel shadows uses ground truth vessel shadow regions identified by expert graders at the Vienna Reading Center (VRC). The results presented here are intended to show the feasibility of this method for the accurate and precise extraction of suitable retinal vessel shadows from multiple vendor 3D SD-OCT scans for use in intra-vendor and cross-vendor 3D OCT registration, 2D fundus registration and actual retinal vessel segmentation. The resulting percentage of true vessel shadow segments to false positive segments identified by the proposed system compared to mean grader ground truth is 95%.