AIM: To evaluate the efficacy of natamyc in curing fungal corneal ulcer by a case-control study of natamyc and fluconazole. METHODS: Eighty-four cases with fungal corneal ulcer were divided into two groups with 42 cases in each group. Natamyc and fluconazole were used for each group respectively. RESULTS: Twenty-one cases were cured, 34 cases were effectively and 8 cases were ineffective, the effective rate was 81% in natamyc group.In fluconazole group, the corresponding number of cases was 11,29,13 respectively, and the effectively and ineffectively,effective rate was 69%. There was no significant difference between the two groups in effective rate (χ2=1.587,P>0.05);there was a significant difference between the two groups in cure rate (χ2=5.048,P<0.05),and also a significant difference between the two groups in average period of therapy which was 16.7±7.68 days in natamyc group and 28.6±7.3 days in fluconazole group (t=7.94, P<0.01). CONCLUSION: Natamyc is more effective than fluconazole in treatment of fungal corneal ulcer, which can be generalized in clinic.