This article presents a cost-effectiveness analysis of colorectal cancer screening tests that have been recommended by the United States Preventive Services Task Force, American Cancer Society US Multi-Society Task Force on Colorectal Cancer American College of Radiology, or the American College of Gastroenterology. This cost-effectiveness analysis supports a common theme of the 3 guideline groups that there are multiple acceptable colorectal cancer screening strategies (including colonoscopy). The article shows which recommended strategies are also cost-effective given a range of willingness to pay per life-year gained. The set of cost-effective strategies includes tests that primarily detect cancer early (annual sensitive fecal occult blood tests [FOBTs]; either guaiac or fecal immunochemical tests, but not Hemoccult II), as well as those that can prevent colorectal cancer (flexible sigmoidoscopy every 5 years with a frequent sensitive FOBT [but not flexible sigmoidoscopy as a standalone test], and colonoscopy). Computed tomographic colonography was not a cost-effective strategy. Stool DNA testing was not assessed in the analysis for this article.