Epidemic keratoconjunctivitis (EKC) is a highly contagious infectious ocular disease that has been widespread worldwide. Ophthalmic preparations of glucocorticoids (OPGs) are the supportive therapies for EKC; however, they are still controversial.We performed a systematic review and meta-analysis to evaluate the efficacy and safety of OPGs in patients with EKC. Electronic searches were conducted in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, China National Knowledge Internet (CNKI), and Wanfang Database from inception to 25 Aug 2022. We included and analyzed randomized controlled trials (RCTs) and cohort studies that compared OPGs to other positive drugs or placebo in patients with EKC.Six studies (five RCTs and one retrospective cohort) involving 286 patients were included in the analysis. Compared with artificial tears, OPGs could relieve ocular symptoms faster in the acute phase of epidemic keratoconjunctivitis (AEKC). There was no significant difference in the incidence of corneal subepithelial infiltrates (SEIs) in AEKC when OPGs were used for 7 days, but there was a substantial difference for 21 and 28 days. In the chronic phase of epidemic keratoconjunctivitis (CEKC), there was no significant difference in the rate of complete elimination of SEIs at 6 months of OPGs treatment compared with immunosuppressants [RR = 1.07,95%CI (0.71,1.61), p = 0.75], as well as in the recurrence rate of SEIs after 6 months [RR = 2.05,95%CI (0.82,5.12), P = 0.13]. OPGs significantly increased intraocular pressure (IOP) at 6 months compared with immunosuppressants [MD = - 1.13,95%CI (- 1.97, - 0.30), P = 0.007]. There was no significant difference in cessation of therapy due to drug intolerance between OPGs and immunosuppressants [RR = 0.69,95%CI (0.16,2.94), p = 0.62].OPGs might relieve ocular symptoms and reduce the incidence of SEIs in AEKC, whereas not recommended the therapy in CEKC. More high-quality clinical evidence is required to confirm our findings.© 2022. The Author(s), under exclusive licence to The Drug Information Association, Inc.