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Background: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide diffusion, but there is no definitive evidence on the factors associated with the failure of mapping. Objectives: To analyze the factors associated with the possible failure of bilateral SLN mapping with indocyanine green (ICG). Methods: A prospective observational study without control on 110 patients with endometrial cancer apparently confined to the uterus, underwent laparoscopic surgical staging with SLN mapping with ICG. Results: Possible risk factors associated with bilateral mapping failure were analyzed, and a multivariate analysis was performed. The bilateral detection rate for SLNs mapping was 72.7%, whereas at least one SLN was detected in 79.1% of patients. No SLNs were identified in 6.3%. None of the patients or features related to tumor were associated with a risk of failure of the method. The only factor analyzed that was significantly associated with the success of bilateral mapping was the surgeon (p = 0.003). Conclusions: Neither obesity nor the presence of lymph node metastases was associated with mapping failure. However, there remains a need for further studies to understand all the mechanisms linked to the unsuccessful method results and to reduce the use of systematic lymphadenectomy in the case of mapping failure.