The incidence of endometrial pathology is increased in women with tamoxifen-induced post-menopausal bleeding (PMB). The aim of this study was to determine the accuracy of transvaginal ultrasound (TVS) in diagnosing endometrial pathology in symptomatic women taking tamoxifen, using endometrial thickness measurements (5 mm and 10 mm cut-offs) and morphological changes within the uterine cavity to define abnormality. The sensitivity of TVS was 97% (95% confidence interval (CI) 83% to 100%) and the specificity 35% (95% CI 17% to 56%) at a 5 mm threshold. The corresponding likelihood ratios for a positive test were 1.47 (95% CI 1.16-2.10) and a negative test were 0.09 (95% CI 0.02-0.53). The use of a higher 10 mm threshold, characterization of endometrial morphology or combining endometrial thickness and morphology did not improve overall accuracy. TVS measurement of endometrial thickness using a 5 mm cut-off is highly accurate in excluding endometrial disease in symptomatic women taking tamoxifen and may negate the need for further diagnostic testing in women unless symptoms recur. A positive TVS result is of little value, so further testing is mandatory in order to detect benign and malignant endometrial disease associated with tamoxifen and PMB.