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Background The usefulness of currently available colon imaging tests, including air contrast barium enema (ACBE), computed tomographic colonography (CTC), and colonoscopy, to detect colon polyps and cancers is uncertain. We aimed to assess the sensitivity of these three imaging tests.Methods Patients with faecal occult blood, haematochezia, iron-deficiency anaemia, or a family history of colon cancer underwent three separate colon-imaging studies—ACBE, followed 7–14 days later by CTC and colonoscopy on the same day. The primary outcome was detection of colonic polyps and cancers. Outcomes were assessed by building an aggregate view of the colon, taking into account results of all three tests.Findings 614 patients completed all three imaging tests. When analysed on a per-patient basis, for lesions 10 mm or larger in size (n=63), the sensitivity of ACBE was 48% (95% CI 35–61), CTC 59% (46–71, p=0·1083 for CTC vs ACBE), and colonoscopy 98% (91–100, p<0·0001 for colonoscopy vs CTC). For lesions 6–9 mm in size (n=116), sensitivity was 35% for ACBE (27–45), 51% for CTC (41–60, p=0·0080 for CTC vs ACBE), and 99% for colonoscopy (95–100, p<0·0001 for colonoscopy vs CTC). For lesions of 10 mm or larger in size, the specificity was greater for colonoscopy (0·996) than for either ACBE (0·90) or CTC (0·96) and declined for ACBE and CTC when smaller lesions were considered.Interpretation Colonoscopy was more sensitive than other tests, as currently undertaken, for detection of colonic polyps and cancers. These data have important implications for diagnostic use of colon imaging tests.