The objective of this study was to assess the effectiveness of saline contrast sonohysterography (SCSH) as a first-line investigation for perimenopausal women with uterine bleeding. A total of 162 women were enrolled in a prospective study. They underwent SCSH indicated for abnormal uterine bleeding. Patients with normal or atrophic endometrium were scheduled for diagnostic hysteroscopy or hormone therapy. Patients with uterine cavity abnormalities were scheduled for surgery (operative hysteroscopy or hysterectomy). A clinical follow-up was obtained for all the patients after SCSH. Sonohysterographic findings were compared with pathological results. SCSH was carried out in 159 patients. In all but one case, the procedure was well tolerated by the patients. There were no complications either during or after the examination. Surgical and pathological results were available in 109 cases. SCSH was highly sensitive and specific in the differentiation between women with intrauterine lesions and those with normal or atrophic endometrium (98.9% and 76.4%, respectively). SCSH was also accurate in the diagnosis of polyps and submucosal myomas (sensitivity 87.8 and 89.6%, specifically 90.7 and 95%). SCSH and surgery displayed the same reliability in the measurement and the localization of the lesions. SCSH recognized endometrial cancer in only 40% of cases. However, all these patients had abnormalities at sonohysterography which indicated a surgical exploration, leading to a zero false-negative rate. Saline contrast sonohysterography appears to be a reliable tool for the investigation of abnormal uterine bleeding in perimenopausal women. It can distinguish women who only require medical therapy from those who require surgery. The method is easy to learn, and is well tolerated by the patients.