OBJECTIVE: This study aimed to assess the value of a randomized controlled trial (RCT) of lymph node dissection (LND) at the time of hysterectomy for high-risk subsets of women with endometrial cancer. METHODS: A modified Markov decision model compared routine LND to no LND for women with grade 3 or grades 2-3 endometrial cancer. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity and value of information (VOI) analyses. Survival without LND was modeled from Surveillance, Epidemiology and End Results program data. A hazard ratio (HR) describing survival in the high-risk group undergoing LND (estimate 0.9, 95% CI 0.6-1.1), adverse event rates, probability and type of adjuvant therapy were modeled from published RCTs. Costs were obtained from national reimbursement data. VOI estimated the value of reducing uncertainty regarding the survival benefit of LND. RESULTS: For grade 3, LND had an incremental cost-effectiveness ratio of $40,183/quality-adjusted life year (QALY) compared to no LND. Acceptability curves revealed considerable uncertainty, with an expected value of perfect information of $4,195 per patient at societal willingness to pay of $50,000/QALY. The estimated value of partial perfect information regarding the HR was $3,702 per patient. Assuming 8,000 individuals annually with grade 3 endometrial cancer in the US, the upper limit of VOI for the HR was $29.6 million annually. For grades 2 and 3 combined, analysis revealed a much lower likelihood of finding LND cost-effective. CONCLUSION: A clinical trial defining the survival effect of LND in women with grade 3 endometrial cancer is a worthwhile use of resources.