Purpose To investigate the relationship between self-reported bupropion use and self-reported glaucoma in a nationally representative sample of the US population. Methods This cross-sectional study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, age ≥40 years, who responded to a question regarding their glaucoma status. Participants were interviewed regarding the use of prescription medications, and those ascertained as having used bupropion were further divided into groups based on duration of usage. Other relevant information, including demographics, comorbidities and health-related behaviours, was obtained via interview. Multivariate logistic regression was performed to determine the OR and 95% CIs for association between bupropion use and prevalent glaucoma. Covariates in the final multivariate model included parameters associated with glaucoma at ptextless0.1: age, gender, ethnicity and annual income. Results 453 participants self-reported a diagnosis of glaucoma, and 108 reported bupropion medication use. Participants who reported using bupropion for more than 1 year had decreased odds of self-reporting a diagnosis of glaucoma (unadjusted OR=0.5, 95% CI 0.01 to 0.52; adjusted OR=0.1, 95% CI 0.01 to 0.81) compared with those not using bupropion or using it for less than a year. Conclusions Bupropion use, particularly for an extended period of time, may be associated with a reduced risk of glaucomatous disease.