Mammographic density has been established as a strong risk factor for breast cancer while use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) has been associated with a reduction in risk of breast cancer. The hypothesis is that NSAIDs reverses the expression of prostaglandin E2, thereby reducing the local production of estrogens. This report describes the differences in mammographic densities by duration of NSAID use in a multiethnic population. Information for this analysis was available from two previous investigations: a nutritional intervention study with 218 women and a nested case-control study of breast density with 1274 women. On the basis of self-reported medication use from a questionnaire common to both investigations, women were categorized into no use, up to 1 year, 2-5 years, 6-10 years, and 11+ years. Screening mammograms were assessed for density using a computer-assisted method. We applied general linear models to calculate mean percent densities for each medication use category while adjusting for covariates. The analysis of the overall study population did not show a significant association between total NSAID use and mammographic density. Contrary to our hypothesis, women with long-term total NSAID use had non-significantly higher densities than non-users. In addition, the results differed by menopausal status. Whereas the trend of higher densities with longer duration of total NSAID use was significant among postmenopausal women, breast density was slightly lower among premenopausal women with long-term NSAID use. Experimental studies need to be performed to study the effect, if any, of NSAID use on breast density.