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Background: Precise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort., Methods: Vimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases., Results: Vimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16-2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13-2.95, P = 0.014)., Conclusions: Loss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions., (© 2024. The Author(s).)