PURPOSE: To describe the ophthalmic manifestations of immune reconstitution inflammatory syndrome (IRIS) associated with Cryptococcus neoformans. METHODS: Four HIV-positive patients on highly active anti-retroviral therapy (HAART) presented with marked optic disk swelling. RESULTS: Three months after the episode of IRIS, 2 of the patients maintained 20/20 visual acuity whose elevated intracranial pressure (ICP) was successfully managed, while 2 patients visual acuities were worse than 20/400 whose ICP was persistently elevated. CONCLUSION: Cryptococcus is another opportunistic infectious organism associated with IRIS with ophthalmic manifestations. Ophthalmologists have the opportunity to play a key role in the early diagnosis and management to prevent serious visual loss.