OBJECTIVE: To estimate the cost-effectiveness of the levonorgestrel intrauterine device (IUD) as an endometrial cancer prevention strategy in obese women. METHODS: A modified Markov model was used to compare IUD placement at age 50 with usual care among women with a body mass index (BMI, kg/m) 40 or greater or BMI 30 or greater. The effects of obesity on incidence and survival were incorporated. The IUD was assumed to confer a 50% reduction in cancer incidence over 5 years. Costs of IUD and cancer care were included. Clinical outcomes were cancer diagnosis and deaths from cancer. Incremental cost-effectiveness ratios were calculated in 2015 U.S. dollars per year of life saved. One-way and two-way sensitivity analyses and Monte Carlo probabilistic analyses were performed. RESULTS: For a 50 year old with BMI 40 or greater, the IUD strategy is costlier and more effective than usual care with an incremental cost-effectiveness ratio of $74,707 per year of life saved. If the protective effect of the levonorgestrel IUD is assumed to be 10 years, the incremental cost-effectiveness ratio decreases to $37,858 per year of life saved. In sensitivity analysis, a levonorgestrel IUD that reduces cancer incidence by at least 68% in women with BMIs of 40 or greater or costs less than $500 is potentially cost-effective. For BMI 30 or greater, the incremental cost-effectiveness ratio of IUD strategy is $137,223 per year of life saved compared with usual care. In Monte Carlo analysis, IUD placement for BMI 40 or greater is cost-effective in 50% of simulations at a willingness-to-pay threshold of $100,000 per year of life saved. CONCLUSION: The levonorgestrel IUD is a potentially cost-effective strategy for prevention of deaths from endometrial cancer in obese women.