Objective: The mechanism by which nonarteritic anterior ischemic optic neuropathy (NAION) causes an infarct in the optic nerve is controversial. We studied the three-dimensional anatomic configuration of a NAION infarct to better elucidate its pathophysiology. Design: Case report with clinicopathologic correlation. Methods: Serial sections of the optic nerve from a previously reported patient diagnosed with NAION 20 days before death were studied. Every fourth slide was stained with hematoxylin-eosin, photographed, and digitized. NIH Image 1.62 was used to reconstruct the nerve in all three dimensions, and the infarct morphology was analyzed. Main Outcome Measures: Morphology of the reconstructed optic nerve infarct. Results: The area of axonal loss within each section of the optic nerve was identified and reconstructed. The loss was in the superior part of the nerve, encircling the central retinal artery at its greatest extent. Remaining areas of the nerve appeared healthy, and, notably, the periphery of the uninvolved inferior portion of the nerve was normal. Three-dimensional analysis revealed two distinct areas of infarct at the posterior extent of the lesion which coalesced toward the center of the lesion and finally tapered as the infarct reached the optic nerve head. Sagittal reconstructions gave the appearance of a two-pronged fork posteriorly connecting to a single "handle" anteriorly. There was no obvious correlation between the configuration of the infarct and any single vascular territory. The total length of the nerve involved by the infarct was approximately 1.5 mm. Conclusions: The morphology of this NAION infarct is not consistent with disease of large or small vessels and, more likely, represents a form of compartment syndrome that causes tissue ischemia.