OBJECTIVE: To assess the diagnostic value of transvaginal sonographic (TVS) measurement of endometrial thickness for diagnosing focal intrauterine pathology in women without abnormal uterine bleeding (AUB). METHODS: A random selection from the Danish Civil Registration System was made: 1660 women aged 20-74 years were invited to participate and 686 women were eligible and accepted inclusion (429 pre- and 257 postmenopausal). The women underwent TVS measurement of endometrial thickness and saline contrast sonohysterography (SCSH). Hysteroscopic resection with histopathology (gold standard) was performed when focal intrauterine pathology was suspected at SCSH. We excluded women with AUB (n = 237), failure of SCSH (n = 50), a scan that was not in the follicular phase (n = 11), hysteroscopy contraindicated (n = 2), and users of sequential hormone therapy (n = 9) or selective estrogen receptor modulators (n = 2). Thus, 375 women without AUB were included (217 pre- and 158 postmenopausal). Receiver-operating characteristics (ROC) curves for endometrial thickness and focal lesion were analyzed. RESULTS: Focal intrauterine pathology was confirmed in 41 women (35 with polyps, five with submucosal myomas and one with polypoidal growing cancer). For premenopausal women, the area under the ROC curve (AUC) was 0.79 (95% CI, 0.68-0.89) and for postmenopausal women it was 0.84 (95% CI, 0.76-0.92). For premenopausal women, the best negative likelihood ratio (LR- = 0.11) was obtained at an endometrial thickness of 5.2 mm, with a negative predictive value (NPV) of 99% and a positive predictive value (PPV) of 10%. For postmenopausal women the best LR- (0.08) was obtained at an endometrial thickness of 2.8 mm, with a NPV of 99% and a PPV of 26%. CONCLUSIONS: In women without AUB, TVS measurement of endometrial thickness is a poor diagnostic test, but is apparently efficacious in excluding focal intrauterine pathology, especially in postmenopausal women. The 4-5-mm threshold conventionally used to exclude endometrial malignancy in women with postmenopausal bleeding is not transferable to women without AUB for excluding focal intrauterine pathology.