Background and aim: In spite of many side effects of corticosteroids on patients, they are commonly used for vernal KERATOCONJUNCTIVITIS (VKC) treatment. Corneal morbidity along with steroid related complications may lead to permanent visual impairment. Therefore, the aim of this study was to evaluate the effect and safety of low dose of topical mitomycin C (MMC) on VKC. Methods: In this randomized clinical trial study, 25 cases of vernal KERATO CONJUNCTIVITIS that had been referred to ophthalmology clinic of Shahrekord Medical University were selected and divided into two groups. Group 1 received mitomycin C 0.01% (n=13) and group 2 received placebo (n=12) 3 times per day for two weeks. Symptoms (Itching, foreign body sensation tearing, photophobia, discharge) & signs (hyperemia punctuate kereatitis, trantas spots and limbal edema) were recorded on the day of presentation, 2 & 4 weeks after treatment period. Mann Whitney test was used to evaluate severity of symptoms and signs in 2 groups. Results: No statistically significant difference was observed in severity of symptoms and signs at the time of presentation between two groups. After two weeks treatment, patients in the MMC group showed significant decrease in photophobia, tearing, foreign body sensation, discharge, hyperemia, punctuate kereatitis, limbal edema and trantas spots compared to the placebo group (P<0.05). No adverse effect of MMC was observed after two weeks. Conclusion: Short term usage of low dose of topical MMC is an effective and safe way to control acute exacerbations in patients with severe VKC.