The aim of this study was to compare the confidence of experienced radiologists in excluding colonic neoplasia with CT colonography (CTC) compared with barium enema. 78 patients (median age 70 years, range 61-87 years, 44 women) underwent same day CTC and barium enema. Two radiologists experienced in reporting barium enema assessed whether the examination had excluded a polyp 6 mm or greater as "yes", "probably" or "no" for each of 6 colonic segments. Two different radiologists experienced in CTC independently performed the same assessment on the CT datasets. Responses were compared using a paired exact test. Formal barium enema and CT reports were compared with any endoscopic examination performed within 1 year. Studies reporting polyps 6 mm+ in patients not subsequently undergoing endoscopy were reviewed by two independent observers. Radiologists stated they had confidently excluded a significant lesion in 314 (71%) and 382 (86%) of 444 segments with barium enema and CTC, respectively (p<0.001). Confidence was significantly higher with CTC in the in the descending and ascending colon (p = 0.02 and p<0.001, respectively), and caecum (p<0.001). 22 patients underwent some form of endoscopy. Of five patients with proven colorectal neoplasia (including two with cancer), CTC and barium enema correctly identified five and three, respectively. In 56 patients not undergoing endoscopy, CTC reported 17 polyps 6 mm+, of which 16 were retrospectively classified as definite or probable. 11 could not be identified on the barium enema, even in retrospect. Confidence in excluding polyps 6 mm or larger is significantly greater with CT colonography particularly in the proximal colon.