OBJECTIVE: We sought to compare the combined diagnostic reliability of sonohysterography and endometrial biopsy with fractional curettage with hysteroscopy in the initial evaluation of postmenopausal women with abnormal uterine bleeding. STUDY DESIGN: This year-long, prospective, controlled, clinical investigation was initiated Sept. 1, 1995. All postmenopausal women with abnormal uterine bleeding were offered inclusion, with 104 enrolled. An endometrial biopsy was performed at the time of initial evaluation. Routine transvaginal ultrasonography was then used to measure the uterus, ovaries, and endometrial stripe thickness, followed immediately by sonohysterography to evaluate the symmetry of endometrial wall thickness and delineate any intraluminal masses. Definitive histopathologic sampling was obtained by fractional curettage with hysteroscopy and statistically compared with the diagnoses arrived at by endometrial biopsy and sonohysterography. RESULTS: The combination of endometrial biopsy and transvaginal sonohysterography positively correlated with the surgical findings >95% of the time, with a sensitivity and specificity of 94% and 96%, respectively (confidence interval 91% to 99%). No patients with endometrial hyperplasia or cancer were misdiagnosed. CONCLUSIONS: Sonohysterography combined with endometrial biopsy is a reliable office tool for evaluating postmenopausal women with abnormal uterine bleeding. Medical management of those patients identified as having no endometrial abnormalities can be considered with confidence, while saving the cost and surgical risk of fractional curettage. Patients with intraluminal masses should be referred for surgical management in a timely fashion. (Am J Obstet Gynecol 1998;178:956-61.)