BACKGROUND: Flexible sigmoidoscopy with polypectomy reduces the incidence of colorectal cancer by removal of premalignant lesions. Factors that reduce the area examined by flexible sigmoidoscopy may reduce its benefit. The aim of this study was to determine whether hysterectomy affects completion and polyp detection rates at flexible sigmoidoscopy. METHODS: Within the setting of a multicenter, prospective, controlled trial of screening flexible sigmoidoscopy, patient and examination variables were compared by appropriate statistical methods for women between the ages of 55 and 64 years with and without a history of a hysterectomy. RESULTS: One quarter of women participants had undergone a hysterectomy. These women were more likely to have incomplete examinations (risk ratio [RR] of incomplete examination, 1.53; 95% CI [1.4, 1.6]). Flexible sigmoidoscopy was more difficult (p <0.001), more painful (p <0.001), and less extensive (46 cm vs. 48 cm insertion on average; p <0.0001) in women who had undergone a hysterectomy. There was a significant trend toward lower relative detection rates of polyps and adenomas at more proximal sites (rectum, sigmoid colon, and proximal to sigmoid; respectively, p = 0.008, p = 0.009) in this group. CONCLUSIONS: Women who have undergone a hysterectomy have less extensive flexible sigmoidoscopy examinations, which are more difficult and more painful, than women without a hysterectomy. Hysterectomy is associated with a reduction in polyp detection rate in the sigmoid colon. This modality of screening may be less effective in women who have undergone a hysterectomy.