The authors describe one patient with essential thrombocytosis and one with chronic hepatitis C infection who developed bilateral simultaneous anterior ischemic optic neuropathy within 3 months of starting treatment with interferon-α. One patient had several typical risk factors for conventional AION; the other did not. These cases are the fourth and fifth reported examples of this phenomenon. Interferon-α treatment may cause or aggravate the risk of developing anterior ischemic optic neuropathy. Vulnerable patients should be advised of this potential complication, assisted in reducing risk factors, and monitored for optic nerve and retinal vascular complications.