ObjectiveTo evaluate the success and failure rate of photoactivated chromophore for keratitis—corneal cross‐linking (PACK‐CXL) therapy in a single population of dogs and cats. To identify the usefulness of the PACK‐CXL based on ulcer depth and establish a cutoff at which this procedure could be recommended. To analyze the influence of the different variables in corneal healing time and to report the presence of secondary endothelial damage and cataract formation.Materials and MethodsMedical records of dogs and cats with presumptive infectious keratitis which underwent accelerated epithelium‐off PACK‐CXL between 2016 and 2023 were reviewed and analyzed.ResultsRecords for 369 animals were included, and the overall success rate for healing was 97% (range 4–74 days and no rescue procedure). The second success (re‐epithelialization <30 days and no rescue procedure) rate was 86%, and a total of 40 eyes needed more than 1 month for the corneal repair. Corneal ulcers were classified in three categories based on the depth: 0%–33% (46%), 34%–66% (37.4%), and 67%–100% (16.5%). The cutoff at which PACK‐CXL had a higher probability of failure was with ulcer depth >66.5%. Animals who suffered from keratomalacia and hypopyon at presentation, or were treated with topical serum or gentamicin after PACK‐CXL showed an increase in epithelial healing time (EHT). Increasing age, brachycephalic conformation, keratomalacia alone, and deeper ulcers were identified as risk factors for the treatment outcome. Secondary endothelial injury or cataract formation was not noted in this study.ConclusionsAccelerated PACK‐CXL is a non‐invasive, adjunctive treatment to medical therapy, which can be used in presumed infectious keratitis with a high probability of success. However, it is important to take in consideration the patient age, skull conformation, presence of keratomalacia, and the ulcer depth.