Background & Aims: Effective colonoscopic screening for polyps, whether by optical or virtual means, requires adequate visualization of the entire colonic surface. The purpose of this study was to assess prospectively the degree of surface coverage at 3-dimensional (3D) endoluminal computed tomography colonography (CTC) after retrograde fly-through, combined retrograde-antegrade fly-through, and review of remaining missed regions. Methods: The study group consisted of 223 asymptomatic adults (mean age, 57.8 ± 7.2 y; 111 men, 112 women) undergoing primary CTC screening. CTC studies were interpreted by experienced readers using a primary 3D approach. The CTC software system that was used continually tracks the percentage of endoluminal surface visualized. The degree of coverage was assessed prospectively after retrograde and combined retrograde-antegrade navigation. The added effect of reviewing missed regions was also assessed prospectively. Results: The mean surface coverage after only retrograde 3D endoluminal fly-through from rectum to cecum was 76.6% ± 4.8% (range, 63%-92%); coverage was 80% or less in 181 (81.2%) patients. Antegrade navigation back to the rectum increased the overall coverage to 94.1% ± 2.3% (range, 84%-99%; P < .0001). A review of missed regions 300 mm2 or larger increased coverage to 97.9% ± 1.1% (range, 93%-99%; P < .0001) and added 21.4 ± 11.4 seconds to the interpretation time (range, 3-67 s). Conclusions: Combined bidirectional retrograde and antegrade 3D navigation, supplemented by rapid review of missed regions, effectively covers the entire evaluable surface at CTC. Unidirectional retrograde 3D fly-through typically excludes 20% or more of the endoluminal surface, which may provide insight into potential limitations at optical colonoscopy.