© 2018, Springer Science+Business Media B.V., part of Springer Nature. Purpose: To report on a keratoconus (KC) patient with Axenfeld-Rieger syndrome (ARS) who developed sterile keratitis after accelerated corneal collagen cross-linking (CXL). Methods: An 18-year-old patient with ARS and KC who had previously undergone intrastromal ring segment implantation underwent accelerated CXL (9 mW/cm 2 UVA intensity for 10 min). Results: After uneventful surgery, the patient presented with severe photophobia, redness of the eye, and decreased vision 72 h following the procedure. Slit-lamp examination showed anterior multiple superficial stromal infiltrates in the central cornea with an overlying epithelium defect. Due to the lack of pain and absence of any pathogen from corneal samples, a diagnosis of sterile keratitis was considered. A combination of topical antibiotic and corticosteroid regimen was administered. Three months after CXL slit-lamp examination showed a mild stromal scar overlying the central cornea, which did not decrease visual acuity. Conclusions: The mechanism by which the sterile keratitis occurs following CXL remains unclear. For our case, the reason of post-CXL sterile keratitis could be considered as an immune response due to the staphylococcal antigens. Furthermore, the possible developmental disturbance of corneal stroma in ARS might have contributed to the development of post-CXL sterile keratitis.