Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485).