Objective: To evaluate the efficacy of saline infusion sonohysterography as a primary screening tool in cases of postmenopausal bleeding and correlate the results with the findings of histopathological examination. Materials and methods: This prospective observational study involved 34 postmenopausal patients with postmenopausal bleeding who attended the OPD of Obstetrics and Gynaecology at Deenanath Mangeshkar Hospital over a period of 4 years and were advised saline infusion sonohysterography (SIS). All women underwent transvaginal sonography (TVS) and saline infusion sonohysterography (SIS) followed by histopathological examination. The sensitivity, specificity, PPV, and NPV for TVS and SIS were analyzed using the HPE report as a gold standard. The advantages and limitations of the screening test were evaluated. Results: The most common abnormalities detected on SIS were thickened endometrium seen in 13 cases (38.2%), followed by polyps (11 cases, 32.4%), thin endometrium (6 cases, 17.6%), submucous fibroids (3 cases, 8.8%), and undetermined (1 case, 2.9%) among our study population with a mean age of 52 ± 7.4 years. Diagnostic accuracy of SIS in identifying patients with intrauterine abnormalities was 91.2%, better than TVS. The sensitivity, specificity, PPV, and NPV of SIS in the detection of intrauterine abnormality was 96.2%, 71.4%, 92.9% and 83.3%, respectively. In this study, the diagnostic accuracy of SIS in identifying patients with abnormal histopathology was 88.2%. Conclusion: Saline infusion sonohysterography can be considered to be a valuable tool in the early workup of postmenopausal bleeding as it is an outpatient, lesstime-consuming procedure and noninvasive with no requirement for anesthesia. Clinical significance: Saline infusion sonohysterography is a sensitive tool and is superior to TVS used alone for evaluation of the uterine cavity. Saline contrast hysterosonography, in combination with HPE if necessary, can become the standard diagnostic procedure in women with postmenopausal bleeding, the gold standard being hysteroscopy.