Purpose To determine the sensitivity and specificity of orbital ultrasonography in distinguishing papilledema from pseudopapilledema in adult patients. Methods The records of all adult patients referred to the neuro-ophthalmology service who underwent orbital ultrasonography for the evaluation of suspected papilledema were reviewed. The details of history, ophthalmologic examination, and results of ancillary testing including orbital ultrasonography, MRI, and lumbar puncture were recorded. Results of orbital ultrasonography were correlated with the final diagnosis of papilledema or pseudopapilledema on the basis of the clinical impression of the neuro-ophthalmologist. Ultrasound was considered positive when the optic nerve sheath diameter was Z3.3 mm along with a positive 301 test. Results The sensitivity of orbital ultrasonography for detection of papilledema was 90% (CI: 80.2-99.3%) and the specificity in detecting pseudopapilledema was 79% (CI: 67.7-90.7%). Conclusions Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive, but less specific in differentiating papilledema from pseudopapilledema in adult patients, and can be useful in guiding further management of patients in whom the diagnosis is initially uncertain.