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Abstract: Objective: The objective of this study is to determine the cost-effectiveness of two strategies in women undergoing surgery for newly diagnosed endometrial cancer. Methods: A decision analysis model compared two surgical strategies: 1) routine lymphadenectomy independent of intraoperative risk factors or 2) selective lymphadenectomy for women with high or intermediate risk tumors based on intraoperative assessment including tumor grade, depth of invasion, and tumor size. Published data were used to estimate the outcomes of stage, adjuvant therapy, and recurrence. Costs of surgery, radiation, and chemotherapy were estimated using Medicare Current Procedural Technology codes and Physician Fee Schedule. Cost-effectiveness ratios were estimated for each strategy. Sensitivity analyses were performed including an estimate for lymphedema for patients that underwent a lymphadenectomy. Results: For 40,000 women diagnosed annually with endometrial cancer in the United States, the annual cost of selective lymphadenectomy is $1.14billion compared to $1.02billion for routine lymphadenectomy. The selective lymphadenectomy strategy cost an additional $123.3million. Five-year progression-free survival was 85.9% in the routine strategy compared to 79.3% in the selective strategy. Treatment cost $6349 more per survivor in the selective strategy compared to routine strategy ($36,078 vs. $29,729). These results held up under a variety of sensitivity analyses including costs due to lymphedema which were higher in the routine lymphadenectomy strategy compared to the selective lymphadenectomy strategy ($10million vs. $7.75million). Conclusions: A strategy of selective lymphadenectomy based on intraoperative risk factors for patients with endometrial cancer was less cost-effective than routine lymphadenectomy even when the impact of lymphedema was considered. [Copyright &y& Elsevier]