PURPOSE: To develop a standardized clinical grading system for the management of patients with vernal keratoconjunctivitis (VKC) and to identify the risk factors associated with a worsened outcome of the disease, including decrease of visual acuity and ocular complications development. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 207 consecutive patients with VKC, referred to our Cornea and External Diseases Center from 1997 to 2007, were included in the study. A total of 110 of those patients were included in the follow-up study (range 1-10 years). METHODS: Classification and regression tree (CART) analysis was performed to separate the patients into 5 subgroups by therapeutic approach. Regression tree and multivariate logistic regression analyses were performed during follow-up to identify predictors of worse visual outcome. MAIN OUTCOME MEASURES: Age, gender, duration and course of disease, signs, symptoms, overall symptoms score, history of atopy, markers of allergy, best-corrected visual acuity, and therapy were collected at baseline and during follow-up. The number of relapses and number of patients with decreased visual acuity were also evaluated in the follow-up. RESULTS: A decision tree for VKC treatment was developed by CART analysis, and a new clinical grading system was proposed accordingly. Sixteen patients were classified as grade 0 (absence of symptoms and no therapy); 59 patients were classified as grade 1 (presence of symptoms without photophobia, occasional use of anti-allergic eye drop); 74 patients were classified as grade 2 (presence of symptoms including photophobia, daily anti-allergic treatment); 22 patients with superficial punctuate keratopathy (SPK) were classified as grade 3 (daily anti-allergic treatment associated with occasional topical steroid); and 36 patients were classified as grade 4 (diffuse SPK or corneal ulcer; pulsed high-dose topical steroid). A higher number of relapses and a higher baseline grade of VKC were the main predictor factors for worse visual outcome. CONCLUSIONS: This grading system allows for identifying the more severe forms of VKC that are at higher risk of recurrences, corneal ulceration, and worse final visual outcome. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.