PurposeTo identify potential factors associated with keratoconus.MethodsThis cross‐sectional study included data from Israel's largest healthcare provider for the years 2005–2020. Keratoconus patients and age‐matched controls were identified. Demographic factors and comorbid conditions, including smoking, diabetes mellitus, asthma, myalgia, mental retardation, Down syndrome, atopic dermatitis and allergy/allergic rhinitis, were compared between the two cohorts. The independent risk factors associated with keratoconus were determined using a multivariable conditional logistic regression model.ResultsOverall, 145 508 subjects were reviewed of which 13 228 were keratoconus patients. A ten‐fold group (n = 132 280) of age‐matched control subjects served as controls for comparisons. In multivariable analysis, several factors were found to be significantly associated with keratoconus. Male gender (OR = 1.27, p < 0.001), Arab ethnicity (OR = 1.50, p < 0.001), diabetes (OR = 1.19, p < 0.001), asthma (OR = 1.50, p < 0.001), myalgia (OR = 1.09, p = 0.02), mental retardation (OR = 2.63, p < 0.001), atopic dermatitis (OR = 1.35, p < 0.001) and allergic rhinitis (OR = 1.21, p < 0.001) were significantly associated with keratoconus. Smoking was significantly protective of keratoconus (OR = 0.66, p < 0.001).ConclusionsThis population‐based study reports male gender, Arab ethnicity, diabetes, asthma, myalgia, mental retardation/Down syndrome, atopic dermatitis and allergic rhinitis as factors associated with keratoconus while smoking demonstrates a protective effect. The results of this study could guide enhanced screening strategies and early interventions, particularly for high‐risk groups.