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CONTEXT: The recommended interval for colorectal cancer screening with flexible sigmoidoscopy (FS) was recently lengthened from 3 to 5 yr. Direct evidence supporting the longer interval is lacking. The appropriateness of the longer interval has been questioned.To compare the incidence of neoplasia detected on FS in individuals who had undergone an FS either 3 yr or 5 yr after a normal examination.DESIGN, SETTINGS, AND PATIENTS: Subjects were drawn from 5,359 individuals who underwent two FS examinations performed for colorectal cancer screening. Examinations were performed by gastroenterologists at a single academic medical center between 1987 and 2002. A total of 2,146 subjects with a normal baseline examination and a follow-up examination 3 and 5 yr later was included.MAIN OUTCOME MEASURE: To compare the incidence of neoplasia, including advanced neoplasia, detected 3 yr versus 5 yr after a normal FS.915 subjects underwent FS at 3 yr and 1,231 subjects at 5 yr after a normal examination. Neoplasia was detected in 3.2% of the 3-yr and 4.3% of the 5-yr subjects (p = 0.17). No significant differences were detected in the pathology, multiplicity, or size of neoplasms between the 3- and 5-yr groups. Advanced neoplasms occurred in 0.9% (including one adenocarcinoma) of subjects at 3 yr and 1.1% of subjects at 5 yr (p = 0.67).Few individuals will develop rectosigmoid neoplasms 3 or 5 yr after a normal FS. The majority of neoplasms detected are low-risk lesions. A screening interval of 5 yr after a normal FS does not portend an increased risk of advanced neoplasms including cancer. This direct evidence supports the current recommendations of a 5-yr interval for colorectal cancer screening with FS.