Background: Colorectal cancer is a significant cause of death. Removal of precancerous adenomas, and early detection and treatment of cancer, has been shown to reduce the risk of death. The aim of this review and meta-analysis was to determine whether flexible sigmoidoscopy (FS) is an effective population screening method for reducing mortality from colorectal cancer. Methods: MEDLINE (1946 to December 2012) and Embase (1980-2012, week 15) were searched for randomized clinical trials in which FS was used to screen non-symptomatic adults from a general population, and FS was compared with either no screening or any other alternative screening methods. Meta-analysis was carried out using a random-effects Mantel-Haenzsel model. Results: Twenty-four papers met the inclusion criteria, reporting results from 14 trials. Uptake of FS was usually lower than that for stool-based tests, although FS was more effective at detecting advanced adenoma and carcinoma. FS reduced the incidence of colorectal cancer after screening, and long-term mortality from colorectal cancer, compared with no screening in a selected population. Compared with stool-based tests in a general population, FS was associated with fewer interval cancers. Conclusion: FS is efficacious at reducing colorectal cancer mortality compared with no screening. It is more effective at detecting advanced adenoma and carcinoma than stool-based tests. FS may be compromised by poorer uptake. Introduction of FS as a screening method should be done on a pilot basis in populations in which it is not currently used, and close attention should be paid to maximizing uptake. The relative risk of adverse events with FS compared with stool-based tests should be quantified, and its real-world effectiveness evaluated against the most effective stool-based tests.