Background: Endometrial cancer (EC) is a common gynecologic malignancy marked by ever-increasing incidence. This study primarily aimed to evaluate the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and lymphovascular space invasion (LVSI), with the secondary objective to assess NLR's prognostic significance for recurrence-free survival (RFS) in endometrial cancer.

Methods: This single-center retrospective cohort study included 335 endometrial cancer patients at Dongyang Hospital of Wenzhou Medical University from January 2012 to January 2024. Two distinct analyses were conducted: (1) Cross-sectional association analysis using ordinal logistic regression and restricted cubic spline (RCS) modeling to evaluate the relationship between preoperative NLR and LVSI status; (2) Survival analysis using Cox proportional hazards (CPH) modeling to assess NLR's prognostic significance for RFS and examine prognostic interactions between NLR and LVSI status.

Results: Multivariate logistic regression revealed no significant association between NLR and LVSI after comprehensive adjustment (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.77–1.53, p = 0.636). Though exploratory spline modeling showed stable risk estimates across the NLR spectrum, formal statistical testing revealed no significant non-linear relationship (p = 0.465). Survival analysis showed borderline significance in patients with superficial invasion (hazard ratio [HR] = 1.56, 95% CI: 1.00–2.43) for RFS, with consistent prognostic patterns across clinicopathological subgroups (all interaction p > 0.05).

Conclusion: This study revealed no significant association with NLR and LVSI, indicating no independent predictive value of NLR in LVSI risk stratification. However, patients with superficial myometrial invasion may present borderline risk for recurrence LVSI. Multi-center validation studies are needed to verify the prognostic value of NLR for LVSI risk stratification in clinical settings.