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Chalazion may be associated with some local and systemic conditions. We studied the prevalence of various conditions among patients with chalazion.A retrospective observational case–control study of all the members who were diagnosed with chalazion in the Central District of Clalit Health Services in Israel (years 2000–2008; n = 9119) and 9119 age- and gender-matched controls randomly selected from the district members. We calculated the prevalence of various ocular, systemic, and demographic conditions as risk factors for chalazion.Demographically, a significant (P < 0.0001) tendency to develop chalazion was found in the population of lower socioeconomic class, in the population living in urban areas, in young females (10–29 years), in older men (older than 60 years), and in non-Ashkenazi Jews. The following risk factors of chalazion were statistically significant: blepharitis [odds ratio (OR), 6.2], rosacea (OR, 2.9), gastritis (OR, 1.4), anxiety (OR, 1.5), irritable bowel syndrome (OR, 1.7), and smoking (OR, 1.2). Diabetes (OR, 0.8) and hypothyroidism (OR, 0.8) were significantly less prevalent among chalazion patients.Some systemic conditions are significantly more prevalent and some are significantly less prevalent among patients with chalazion. Better understanding of the pathophysiological association between those diseases and chalazion may help in its treatment and prevention.