Objective: Given the improvement in the surgical treatment of endometrial cancer with the inclusion of sentinel lymph node biopsy (SLNB), our aim was to evaluate the impact of this minimally invasive and tailored nodal assessment on patients’ quality of life (QoL). Methods: This was a cross-sectional study conducted in a single-centre, tertiary-level hospital. Patients diagnosed with preoperative early-stage endometrial cancer, who underwent primary surgical treatment between August 2015 and November 2021, were included. The enrolled patients were divided into two cohorts according to the nodal staging performed: the first group underwent only SLNB (SLNB group); the second group underwent pelvic and/or para-aortic lymphadenectomy (LND group). We evaluated the overall QoL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life core 30-item questionnaire (EORTC QLQ-C30) and a sexual health questionnaire (EORTC SHQ-C20). The scores were compared between the groups. Results: Ninety patients were enrolled in the study: 61 (67.8%) in the SLNB group and 29 (32.2%) in the LND group. In the LND group, 24 (82.7%) patients underwent pelvic and para-aortic LND, while 5 (17.3%) patients underwent pelvic LND. The assessment of the functional scales showed better results for the SLNB group than for the LND group, with a significantly lower impact on physical status (8.2% vs. 25%, respectively;p= 0.031). In terms of the symptom scales, the SLNB group reported a significantly lower negative impact on sleep quality (4.9% vs. 27.6%, respectively;p< 0.01), pain (1.6% vs. 13.8%, respectively;p= 0.019), and dyspnoea (0% vs. 10.3%, respectively;p= 0.011) than the LND group. The SLNB group had better results for all analysed items regarding sexual QoL. Conclusions: The implementation of a surgical technique with SLNB improved patients’ overall QoL by increasing their well-being in the functional and symptom spheres.