Penetrating keratoplasty carries an infectious risk. Its requirement for topical corticosteroid therapy facilitates fungal growth with resulting keratitis. Although progression of fungal keratitis to intraocular infection is uncommon, endophthalmitis resulting from keratitis usually has a poor visual prognosis. Fungal infection under these circumstances remains a diagnostic and therapeutic challenge. We report a complicated case of recurrent fungal keratitis with endophthalmitis following a contaminated penetrating keratoplasty that ultimately was controlled with a new treatment modality. Intrastromal corneal injections combined with intravitreal injection of amphotericin B led to the eradication of the corneal fungal plaques and the intraocular infection. Intrastromal corneal injections of amphotericin B may offer a less invasive, in-office alternative to repeat penetrating keratoplasty.