A randomized, controlled trial was performed to compare the diagnostic yields and cost-effectiveness of two strategies for the evaluation of nonemergent lower gastrointestinal bleeding. Three hundred eighty patients aged greater than or equal to 40 yr were randomized to undergo initial flexible sigmoidoscopy plus air contrast barium enema or colonoscopy; 332 completed the initial studies. Initial colonoscopy detected more cases of polyps less than 9 mm in size, adenomas, and arteriovenous malformations but fewer cases of diverticulosis. No significant difference was found between strategies in the number of patients detected with cancers or polyps greater than or equal to 9 mm in size. In both strategies, cancers were more common in subjects aged greater than or equal to 55 yr (8% overall) than in those aged less than 55 yr (1%). Among patients aged less than 55 yr with suspected lower gastrointestinal bleeding, initial flexible sigmoidoscopy plus air contrast barium enema is a more cost-effective strategy for the detection of colonic neoplasms than initial colonoscopy. However, initial colonoscopy is more cost effective for those aged greater than or equal to 55 yr.