A study was conducted to compare transvaginal ultrasound (TVS), saline infusion sonography (SIS) and outpatient hysteroscopy for examining the uterine cavity in women with postmenopausal bleeding and unscheduled bleeding on hormone replacement therapy (HRT). Fourty Subjects agreed to undergo TVS, SIS and hysteroscopy in addition to endometrial sampling. The abnormalities detected by each imaging method were recorded together with the discomfort (visual analogue scale). Thirty women completed all three imaging procedures. In 18 cases TVS suggested an abnormal cavity. SIS and hysteroscopy were of similar efficacy in clarifying the nature of this, and confirmed an abnormality in 12 cases (40%). TVS was significantly less painful than the other procedures (p < 0.001). SIS and hysteroscopy were associated with pain scores similar to endometrial sampling. These findings justify the need for a large randomised trial of TVS, SIS, hysteroscopy and endometrial sampling, in order to develop the most appropriate strategy for investigating postmenopausal bleeding and unscheduled bleeding on HRT.