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Purpose: Aging is a major risk factor in dry eye disease (DED), and understanding sexual differences is very important in biomedical research. However, there is little information about sex differences in the effect of aging on DED. We investigated sex differences in the effect of aging and other risk factors for DED., Methods: This study included data of 16,824 adults from the Korea National Health and Nutrition Examination Survey (2010-2012), which is a population-based cross-sectional survey. DED was defined as the presence of frequent ocular dryness or a previous diagnosis by an ophthalmologist. Basic sociodemographic factors and previously known risk factors for DED were included in the analyses. Linear regression modeling and multivariate logistic regression modeling were used to compare the sex differences in the effect of risk factors for DED; we additionally performed tests for interactions between sex and other risk factors for DED in logistic regression models., Results: In our linear regression models, the prevalence of DED symptoms in men increased with age ( R =0.311, P =0.012); however, there was no association between aging and DED in women ( P >0.05). Multivariate logistic regression analyses showed that aging in men was not associated with DED (DED symptoms/diagnosis: odds ratio [OR] =1.01/1.04, each P >0.05), while aging in women was protectively associated with DED (DED symptoms/diagnosis: OR =0.94/0.91, P =0.011/0.003). Previous ocular surgery was significantly associated with DED in both men and women (men/women: OR =2.45/1.77 [DED symptoms] and 3.17/2.05 [DED diagnosis], each P <0.001). Tests for interactions of sex revealed significantly different aging × sex and previous ocular surgery × sex interactions ( P for interaction of sex: DED symptoms/diagnosis - 0.044/0.011 [age] and 0.012/0.006 [previous ocular surgery])., Conclusion: There were distinct sex differences in the effect of aging on DED in the Korean population. DED following ocular surgery also showed sexually different patterns. Age matching and sex matching are strongly recommended in further studies about DED, especially DED following ocular surgery., Competing Interests: Disclosure The authors report no conflicts of interest in this work.