Endometrial cancer is the most common female genital tract cancer in developed countries. We systematically reviewed the current health-economic evidence on early detection and prevention strategies for endometrial cancer based on a search in relevant databases (Medline/Embase/Cochrane Library/CRD/EconLit). Study characteristics and results including life-years gained (LYG), quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) were summarized in standardized evidence tables. Economic results were transformed into 2019 euros using standard conversion methods (GDP-PPP, CPI). Seven studies were included, evaluating (1) screening for endometrial cancer in women with different risk profiles, (2) risk-reducing interventions for women at increased or high risk for endometrial cancer, and (3) genetic testing for germline mutations followed by risk-reducing interventions for diagnosed mutation carriers. Compared to no screening, screening with transvaginal sonography (TVS), biomarker CA-125, and endometrial biopsy yielded an ICER of 43,600 EUR/LYG (95,800 EUR/QALY) in women with Lynch syndrome at high endometrial cancer risk. For women considering prophylactic surgery, surgery was more effective and less costly than screening. In obese women, prevention using Levonorgestrel as of age 30 for five years had an ICER of 72,000 EUR/LYG; the ICER for using oral contraceptives for five years as of age 50 was 450,000 EUR/LYG. Genetic testing for mutations in women at increased risk for carrying a mutation followed by risk-reducing surgery yielded ICERs below 40,000 EUR/QALY. Based on study results, preventive surgery in mutation carriers and genetic testing in women at increased risk for mutations are cost-effective. Except for high-risk women, screening using TVS and endometrial biopsy is not cost-effective and may lead to overtreatment. Model-based analyses indicate that future biomarker screening in women at increased risk for cancer may be cost-effective, dependent on high test accuracy and moderate test costs. Future research should reveal risk-adapted early detection and prevention strategies for endometrial cancer.