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Simple Summary: Sentinel lymph node (SLN) mapping is safe, feasible, and cost-effective to determine the lymph node status in endometrial cancer (EC). The aim of our prospective SLIM study was to investigate the incidence of SLN metastases and the contribution of SLN mapping in the management of presumed low- and intermediate-risk EC, i.e., clinical early-stage EC, endometrioid histology, grade 1 or 2. SLN metastases were present in 11.2% of 152 patients. Adjuvant management was adjusted based on the SLN status in 7.9% of patients: in 5.9% adjuvant treatment was added due to a positive sentinel node, and in 2.0% adjuvant treatment was limited due to unexpected grade 3 disease with a negative SLN. SLN mapping seems important in patients with presumed low- and intermediate-risk EC and may avoid undertreatment as well as overtreatment. The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (n = 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (n = 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment. [ABSTRACT FROM AUTHOR]