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Purpose: To report a case of syphilitic interstitial keratitis successfully managed with topical tacrolimus after the development of steroid-induced intraocular pressure elevation in a pediatric patient. Observations: A 4-year-old female with a history of congenital syphilis that was reportedly treated after birth presented with bilateral conjunctival redness, tearing, and photosensitivity. Initial ophthalmic examination revealed corneal vascularization with diffuse haze of the right eye and circumferential vascularization with stromal infiltrates of the left eye. She was diagnosed with bilateral syphilitic interstitial keratitis and initially managed with topical steroids but developed steroid-induced elevation of her intraocular pressure. She experienced several recurrences of keratitis as steroids were tapered. After a recurrence in her right eye, she was treated with topical tacrolimus. Since then, she has remained recurrence-free for almost three years with normal intraocular pressure. Conclusion and importance: Tacrolimus represents a novel alternative for the treatment of syphilitic interstitial keratitis, which is particularly useful in patients that develop elevated intraocular pressures in response to long-term treatment with steroid eye drops.