The appropriate interval between negative colonoscopy screenings is uncertain, but the numbers of advanced neoplasms 10 years after a negative result are generally low. We aimed to evaluate the cost-effectiveness of colorectal neoplasm screening and management based on repeat screening colonoscopy every 10 years or single colonoscopy, compared with no screening in the general population. A state-transition Markov model simulated 100,000 individuals aged 50-80 years accepting repeat screening colonoscopy every 10 years or single colonoscopy, offered to every subject. Colorectal adenomas found during colonoscopy were removed by polypectomy, and the subjects were followed with surveillance every three years. For subjects with a normal result, colonoscopy was resumed within ten years in the repeat screening strategy. In single screening strategy, screening process was terminated. Direct costs such as screening tests, cancer treatment and costs of complications were included. Indirect costs were excluded from the model. The incremental cost- effectiveness ratio was used to evaluate the cost-effectiveness of the different screening strategies. Assuming a first-time compliance rate of 90%, repeat screening colonoscopy and single colonoscopy can reduce the incidence of colorectal cancer by 65.8% and 67.2% respectively. The incremental cost-effectiveness ratio for single colonoscopy (49 Renminbi Yuan [RMB]) was much lower than that for repeat screening colonoscopy (474 RMB). Single colonoscopy was a more cost-effective strategy, which was not sensitive to the compliance rate of colonoscopy and the cost of advanced colorectal cancer. Single colonoscopy is suggested to be the more cost-effective strategy for screening and management of colorectal neoplasms and may be recommended in China clinical practice.