Background: The optimal evaluation of young adults with rectal bleeding remains uncertain. In this investigation, we prospectively compare the findings of flexible sigmoidoscopy (FS) and colonoscopy in young patients with rectal bleeding. Methods: Patients aged 18-40 with a history of bright red blood per rectum were prospectively recruited. Patients were excluded if they had melena, hematemesis, iron-deficiency anemia, a positive fecal occult blood test, a history of inflammatory bowel disease (IBD), a first degree relative with colon cancer under age 50, a barium enema that obligated colonoscopy, or colonoscopy within the previous year. Prior to endoscopy, one investigator interviewed and examined the patient and classified the bleeding as outlet, luminal, or indeterminate. A second investigator, who was blinded to the type of bleeding, then performed an unsedated FS to a maximal insertion of 60 cm, as tolerated by the patient. Sedated colonoscopy was then performed immediately thereafter. Findings were recorded following each procedure. Results: 31 patients were considered for inclusion in the study. 17 patients (3M/14F; age range 21-40 yrs, mean 31 yrs) have undergone the investigation. 5 patients were excluded for: iron-deficiency anemia (3), IBD (1), and first degree relative with colon cancer under age 50 (1). 8 patients declined to participate. 1 patient was referred but could not be contacted. 5/17 (29%) patients were classified as outlet bleeding, 2/17 (12%) as luminal, and 10/17 (59%) as indeterminate. The average depth of insertion on FS was 49 cm (range 17-60 cm). FS findings: hemorrhoids 9/17 (53%); anal fissures 4/17 (24%); anal cryptitis 3/17 (18%); ulcerative colitis 2/17 (12%); rectal ulcer 1/17 (6%); and rectosigmoid adenocarcinoma 1/17 (6%). 2 patients (12%) had a negative FS, and 3 patients (18%) had 2 or more findings on FS. Colonoscopy findings: 1 patient (6%) with indeterminate bleeding had diverticulosis and angiodysplasia on colonoscopy but only cryptitis on FS. The other 16 (94%) patients had no additional findings on colonoscopy besides those on FS. Colonoscopy could not be completed in 3 patients (18%) because of looping or patient intolerance. Conclusions: The preliminary results of this prospective comparison of FS and colonoscopy in young adults with rectal bleeding indicate that colonoscopy rarely yields additional diagnoses, even in patients with luminal or indeterminate type bleeding.