Objective To evaluate the prevalence of systemic medical conditions in patients with blepharitis. Design A retrospective observational case-control study. Participants and Controls All the members who were diagnosed with blepharitis in the Central District of Clalit Health Services in Israel (years 20002009; n=16706) and 16706 age- and gender-matched controls randomly selected from the district members. Methods Analysis of the prevalence of various ocular and systemic conditions, risk factors, age, gender, marriage status, country of origin, place of residency, and socioeconomic status. Main Outcome Measures The prevalence of any associated morbidity. Results Demographically, a significantly higher tendency to develop blepharitis was found in populations of lower socioeconomic class, populations living in urban areas, and Ashkenazi Jews. A significant association of P<0.001 was found with some inflammatory diseases (gastritis, peptic ulcer, asthma, arthropathy, and ulcerative colitis), psychologic conditions (anxiety, irritable bowel syndrome, neuroses, and depression), hormonal conditions (hypothyroidism and prostatic hypertrophy), cardiovascular diseases (carotid artery disease, hyperlipidemia, hypertension, and ischemic heart disease), and other eye conditions (chalazion, pterygium). The strongest associations found were between blepharitis and chalazia (odds ratio [OR] 4.7; confidence interval [CI], 3.8-5.7), rosacea (OR 3; CI, 2.1-4.3), pterygia (OR 2.0; CI, 1.5-2.6), ulcerative colitis (OR 2.3; CI, 1.2-4.2), irritable bowel syndrome (OR 1.8; CI, 1.3-2.5), anxiety (OR 1.6; CI, 1.4-1.9), and gastritis (OR 1.6; CI, 1.4-1.7). Conclusions Some ocular and systemic conditions are more prevalent among patients with blepharitis. Better understanding of the pathophysiologic association between those diseases and blepharitis may help in its treatment and prevention. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.