PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.