Registration of endoscopic video to preoperative CT facilitates high-precision surgery of the head, neck, and skull-base. Conventional video-CT registration is limited by the accuracy of the tracker and does not use the underlying video or CT image data. A new image-based video registration method has been developed to overcome the limitations of conventional tracker-based registration. This method adds to a navigation system based on intraoperative C-arm cone-beam CT (CBCT), in turn providing high-accuracy registration of video to the surgical scene. The resulting registration enables visualization of the CBCT and planning data within the endoscopic video. The system incorporates a mobile C-arm, integrated with an optical tracking system, video endoscopy, deformable registration of preoperative CT with intraoperative CBCT, and 3D visualization. Similarly to tracker-based approach, the image-based video-CBCT registration the endoscope is localized with optical tracking system followed by a direct 3D image-based registration of the video to the CBCT. In this way, the system achieves video-CBCT registration that is both fast and accurate. Application in skull-base surgery demonstrates overlay of critical structures (e.g., carotid arteries) and surgical targets with sub-mm accuracy. Phantom and cadaver experiments show consistent improvement of target registration error (TRE) in video overlay over conventional tracker-based registration-e.g., 0.92mm versus 1.82mm for image-based and tracker-based registration, respectively. The proposed method represents a two-fold advance-first, through registration of video to up-to-date intraoperative CBCT, and second, through direct 3D image-based video-CBCT registration, which together provide more confident visualization of target and normal tissues within up-to-date images.