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Early prognostication of the outcome in resuscitated post cardiac arrest (CA) patients remains challenging especially if treated with therapeutic hypothermia. Brain edema caused by hypoxic-ischemic encephalopathy (HIE) can indirectly be estimated by transorbital sonography (TOS) taking in account the optic nerve sheath diameter (ONSD). The prognostic value of this easy, safe, and reproducible technique was investigated in this study.A total of 49 patients, initially unconscious (Glasgow Coma Scale ≤6) after successful resuscitation, were enrolled into this prospective observational study. Sonographic ONSD measurements were performed twice on day of admission (day 0) and once on days 1 and 2 after CA. Beyond ONSD, established prognostic parameters like neuron specific enolase and gray-white matter ratios were assessed. Cerebral Performance Category (CPC) score served as outcome parameter.A total of 15 (31.3%) patients had a good outcome (CPC-score 1–2), 8 patients (14.6%) had severe disability (CPC-score 3–4), and 26 (54.2%) had a fatal outcome (CPC-score 5). Already in the first measurement on day 0, nonsurvivors showed significantly higher ONSD values (P < .001). For predicting mortality, a threshold of 5.75 mm was calculated with a specificity of 100%. ONSD did not differ significantly depending on hypothermia (P = .7009).Early and reliable prognostication of outcomes in patients with HIE can be simplified by ONSD values gathered with the use of TOS. Main advantages compared to other established markers are prognostication within the first 24 hours and independence from therapy with hypothermia. A higher level of accuracy can be reached by combining computed tomography (gray-to-white matter ratio values) and ONSD values.