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Tacrolimus (FK506) is a potent and effective immunosuppressive agent, mainly utilized after solid organ transplantation. We report the clinical features of tacrolimus optic neuropathy (TON) in a patient on tacrolimus therapy that had an exhaustive workup not revealing any additional cause. The patient was a 60-year-old man post-cardiac transplantation who presented with a 5-month history of vision loss OD and 10 days of vision loss OS. Dilated exam showed significant optic disc edema in both eyes (OCT RNFL 442 μm OD and 330 μm OS). Multiple lumbar punctures showed a normal opening pressure. After discontinuation of tacrolimus, he noticed gradual improvement in his vision and 10-month follow-up revealed significantly improved visual function and resolved optic disc edema. This case report adds significant optic disc edema to the clinical characteristics of TON. TON should be suspected in any patient on this medication with a new optic neuropathy and negative workup for infectious or inflammatory causes. Discontinuation of the medication and change to cyclosporine can result in improvement in vision., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by S. Karger AG, Basel.)