Objective. To evaluate the clinical relevance of 3-dimensional saline infusion sonography (3D-SIS) in addition to conventional SIS in women with abnormal uterine bleeding suspected of having intrauterine abnormalities. Methods. All women suspected of having intrauterine abnormalities were eligible. Before 3D-SIS, conventional SIS was performed. The results of these techniques were compared with the "combined method reference standard" (hysteroscopy, endometrial sampling, and clinical followup in cases with normal SIS findings). Diagnostic characteristics (with 95% confidence intervals [CIs]) of 3D-SIS and SIS were calculated as well as their respective accuracy in evaluating the histologic nature, the intrauterine extension, and the location of intrauterine abnormalities. Moreover, the reliability (κ value) and clinical relevance of 3D-SIS were assessed. Results. A total of 49 women were included, and 4 women were excluded. The positive predictive values of 3D-SIS and SIS were, respectively, 1.00 and 0.86 (95% CI, 0.72-0.99; P = .15), and the diagnostic accuracy values were 0.98 (95% CI, 0.94-1.0) and 0.91 (95% CI, 0.83-0.99; P = .08). Saline infusion sonography and 3D-SIS were equally accurate in evaluating the histologic nature, intrauterine extent, and location of intrauterine abnormalities (respective κ values: 0.85 versus 0.93; P = .88; 0.83 versus 0.83; and 0.77 versus 0.80; P = .81). The reliability of 3D-SIS was good: intraobserver and interobserver agreement (κ) were 0.78 and 0.72. Three women (6.7%) had the benefit of additional 3D-SIS: in these women, SIS wrongly led to a diagnosis of intrauterine abnormalities (P = .08). Conclusions. Three-dimensional saline infusion sonography is valid and reliable in women suspected of having intrauterine abnormalities and may indeed have relevant clinical value in addition to conventional SIS.