The authors report a case of nontraumatic orbital subperiosteal hematoma after general anesthesia with patient in the prone position. The patient, who was on aspirin, clopidogrel, and subcutaneous heparin, presented immediately after sacral ulcer debridement with acute bilateral vision loss and periorbital edema. While the OD improved with conservative management, the OS continued to have 20/200 vision, decreased color vision, afferent pupillary defect, and extraocular movement limitation after lateral canthotomy and cantholysis. Imaging revealed bilateral subperiosteal hematomas in the superior orbital roof stretching the posterior optic nerve. Left orbitotomy with drainage of hematoma under anesthesia was then performed, with full resolution of symptoms and recovery of vision to 20/20 by postoperative week 2. While a few cases of orbital subperiosteal hematoma after nonophthalmic surgeries have been previously reported, the majority were in the supine position, unilateral, and resolved without surgical decompression. This case suggests that the increase in venous pressure from prone positioning, especially in patients on anticoagulation or antiplatelet therapy, could contribute to bleeding into the subperiosteal space. Furthermore, although the orbital compartment syndrome and elevated intraocular pressure resolved with canthotomy/cantholysis, there was persistent compressive optic neuropathy that required surgical intervention.