To evaluate the clinicopathological characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening.This was a retrospective study. Postmenopausal women with endometrial thickening (defined as the thickest endometrial portion in the sagittal uterine plane was greater than or equal to 5 mm) through transvaginal ultrasound in our outpatient department, and further referred to the gynecology department at Xuanwu Hospital for hysteroscopic diagnostic curettage assessment between January 2018 and March 2021 were included. According to the histopathological results, participants were divided into the benign group and malignant group. Univariate analysis was used to compare the differences in various factors, including demographics, clinical characteristics, medical complications, and ultrasound characteristics, between the two groups. Multiple logistic regression analysis was used to identify the factors that were independent contributors to the development of endometrial malignancy. Receiver operating characteristic analysis of endometrial thickness (ET) to predict endometrial malignancy was performed.In total, 385 eligible cases were included in the analysis. The results suggested that older age (odds ratio [OR] 1.061, 95% confidence interval [CI] 1.008-1.116, P = 0.023), thicker ET (OR 5.032, 95% CI 2.453-10.322, P < 0.001), irregular menstruation in the past (OR 19.203, 95% CI 1.936-190.431, P = 0.012), postmenopausal bleeding (OR 12.341, 95% CI 4.440-34.302, P < 0.001), and polypoid mass-like lesions (OR 30.330, 95% CI 8.974-102.509, P < 0.001) were risk factors that were independently associated with the development of endometrial malignancy in postmenopausal women with increased ET. The optimal critical value of ET in predicting malignancy was 9.5 mm, and the sensitivity and specificity were 71.70% and 71.69%, respectively.For postmenopausal women with endometrial thickening, our results suggested that women who are older, have a thicker ET, had irregular menstruation in the past, have postmenopausal bleeding, and have polypoid mass-like lesions should seek medical attention as soon as possible and undergo further invasive examination. The use of 9.5 mm as the ET value to prompt investigations may be acceptable since it is unlikely to miss any atypical endometrial hyperplasia or endometrial cancer.Copyright © 2022 by The North American Menopause Society.