Anti-TNF-α agents (e.g. infliximab, adalimumab, etanercept) are effective management options in various inflammatory and autoimmune diseases (e.g. inflammatory bowel disease). The occurrence during anti-TNF-α agent therapy of a new onset or exacerbation of an inflammatory condition that usually responds to this class of drug has been termed a paradoxical adverse event (PAE). A wide range of ophthalmic PAEs have been reported including uveitis, optic neuritis/neuropathy, scleritis, orbital myositis, retinal vasculitis, and others. The patient reported herein developed a dramatic orbital inflammatory PAE during his infliximab infusions, which manifested as an acute orbital apex syndrome with vision loss. Physicians using this medication should be aware of this serious vision-threatening PAE, and urgent therapy with high dose intravenous corticosteroids may be required.