Purpose: The VA Cooperative 380 and the CONCeRN Trial both demonstrated the superior yield of colonoscopy to sigmoidoscopy in average risk individuals undergoing colorectal cancer (CRC) screening. Current consortium guidelines indicate that colonoscopy is the preferred CRC screening test. However, resources are inadequate to provide population colonoscopy screening and alternative methods are needed. Computed tomographic colonography (CTC) is another total colonic examination that has been shown to be as accurate as colonoscopy for the detection of colonic neoplasia 6 mm or larger at our institution. The aim of this study was to determine the prevalence of advanced colonic neoplasia in patients in whom CTC revealed only recto-sigmoid (RS) polyps and to determine the diagnostic yield of only polypectomy via flexible sigmoidoscopy (FS) examination in such patients. Methods: All subjects were participants in a trial in which they underwent both CTC and colonoscopy with segmental unblinding. Patients with only RS findings by CTC were retrospectively identified. Findings at FS were estimated by including only lesions that were identified and removed distal to the descending sigmoid junction during colonoscopy. This anatomic delineation was chosen because several studies have shown that the average endoscopist in a primary care setting is able to reliably examine the colon to the sigmoid-descending colon junction with FS. Pathologic evaluations of any lesions proximal to this point were reviewed. Polyps were classified according to the following criteria: Adenocarcinoma, tubulovillous adenoma, tubular adenoma > 1 cm, and > = 3 tubular adenomas were considered advanced findings. All other lesions were deemed non-advanced. Results: 203 patients had only RS polyps identified on CTC. 64 (32%) of these patients were found to have right sided lesions during colonoscopy. Three (1.5%) of these lesions were advanced neoplastic lesions. Conclusions: Miss rates for advanced lesions with FS after CTC showing only RS lesions are comparable to miss rates for colonoscopy. FS may be used to follow-up CTC which only reveal RS findings with little risk of missing proximal advanced colonic neoplasia. Employing this strategy would decrease the cost and risk of follow-up examinations after CTC. Further study to determine the cost effectiveness of this approach is warranted.