Objective: To investigate off-label ophthalmic medications, and provide an effective and safe evidence-based reference for the rational use of ophthalmic drugs. Methods: On the basis of collecting the off-label drug use recorded in 21 Aier Eye Hospital Group which including ophthalmic central cities and provincial capital level hospitals, and spot checking the prescription and doctor’s order drug use, this article conducted full demonstration and evaluation of off-label drug use which referred to the off-label drug used consensus of Guangdong and Shandong, and other literature on the off-label drug use in ophthalmology. The paper conducted statistics, analysis and induction, and solicited the opinions of relevant ophthalmology clinical experts. Results: Sorting out the evidence of the guides,consensus, journal papers and other evidence-based medicine in ophthalmic medication, recommending 8 items of level 1, 29 items of level 2, and 24 items of level 3, we compiled the “Reference catalogue for the off-label drug use in ophthalmic hospital (2021 edition)” within the group which can providing reference for clinical use. There were 61 off-label drugs commonly used in ophthalmology, involving 32 drugs. Among them, 32 items (52.5%) were used by over administration route, 13 items (21.3%) were used by over indication, and 14 items (23.0%) were used by over indication and administration route. Antibacterial drugs were the most frequently used in the varieties and items of off-label drug use, accounting for 13 (40.6%) and 26 (42.6%) respectively. Conclusion: Ophthalmic off-label medications are common owing to the special route of administration. Such as intraocular injection or eye drop have played a good role in the treatment of some ocular infectious diseases. Standardizing the off-label drug use of ophthalmology is an effective measure to reducing medical risks.