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The safety of endoscopic skull base surgery can be enhanced by accurate navigation in preoperative computed tomography (CT) or, more recently, intraoperative cone-beam CT (CBCT). The ability to register real-time endoscopic video with CBCT offers an additional advantage by rendering information directly within the visual scene to account for intraoperative anatomical change. However, tracker localization error (~1-2 mm ) limits the accuracy with which video and tomographic images can be registered. This paper reports the first implementation of image-based video-CBCT registration, conducts a detailed quantitation of the dependence of registration accuracy on system parameters, and demonstrates improvement in registration accuracy achieved by the image-based approach. Performance was evaluated as a function of parameters intrinsic to the image-based approach, including system geometry, CBCT image quality, and computational runtime. Overall system performance was evaluated in a cadaver study simulating transsphenoidal skull base tumor excision. Results demonstrated significant improvement (p <; 0.001) in registration accuracy with a mean reprojection distance error of 1.28 mm for the image-based approach versus 1.82 mm for the conventional tracker-based method. Image-based registration was highly robust against CBCT image quality factors of noise and resolution, permitting integration with low-dose intraoperative CBCT.