OBJECTIVES:The aim of this study was to determine the cost-effectiveness of family history screening (FHS) for colorectal cancer (CRC) susceptibility at age 40 with early screening of those with increased risk.METHODS:The cost-effectiveness of several family history-based screening programs was estimated with a validated microsimulation model, using data from the SEER cancer registry, life tables, medicare records, and published data. Familial cancer syndromes were excluded. Screening programs evaluated included (i) colonoscopy screening every 10 years starting at age 50 (no family history assessment); (ii) colonoscopy every 10 years from age 40 for persons with a family history; (iii) colonoscopy every 5 years from age 50 for those with a family history; and (iv) colonoscopy every 5 years from age 40 for persons with a family history. In each FHS scenario, persons without a family history are screened with colonoscopy at age 50, then every 10 years to age 80.RESULTS:Compared with colonoscopy screening of all persons from age 50, the cost-effectiveness of the family history-based screening programs varied from $18,000-$51,000 per life year (LY) gained. Screening family history cases every 5 years from age 40 is more cost-effective than screening every 10 years from age 40. Reducing screening frequency for those without a family history lowers program expenditures substantially at a modest loss of LYs. The results are sensitive to the CRC risk difference between positive and negative family histories.CONCLUSIONS:The cost-effectiveness of CRC FHS guidelines varies widely. Economic issues should be considered before implementing family history-directed screening programs.Am J Gastroenterol advance online publication, 11 May 2010; doi:10.1038/ajg.2010.185.