AbstractObjectiveAlthough there is increasing evidence to suggest the cost‐effectiveness of aspirin use to prevent colorectal cancer (CRC) in the general population, no study has assessed cost‐effectiveness in patients with familial adenomatous polyposis (FAP), who are at high risk of developing CRC. We examined the cost‐effectiveness of preventive use of low‐dose aspirin in FAP patients who had undergone polypectomy in comparison with current treatment practice.DesignWe developed a microsimulation model that simulates a hypothetical cohort of the Japanese population with FAP for 40 years. Three scenarios were created based on three intervention strategies for comparison with no intervention, namely intensive downstaging polypectomy (IDP) of colorectal polyps at least 5.0 mm in diameter, IDP combined with low‐dose aspirin, and total proctocolectomy with ileal pouch‐anal anastomosis (IPAA). Cost‐effective strategies were identified using a willingness‐to‐pay threshold of USD 50,000 per QALY gained.ResultsCompared with no intervention, all strategies resulted in extended QALYs (21.01–21.43 QALYs per individual) and showed considerably reduced colorectal cancer mortality (23.35–53.62 CRC deaths per 1000 individuals). Based on the willingness‐to‐pay threshold, IDP with low‐dose aspirin was more cost‐effective than the other strategies, with an incremental cost‐effectiveness ratio of $57 compared with no preventive intervention. These findings were confirmed in both one‐way sensitivity analyses and probabilistic sensitivity analyses.ConclusionThis study suggests that the strategy of low‐dose aspirin with IDP may be cost‐effective compared with IDP‐only or IPAA under the national fee schedule of Japan.