Non-steroidal anti-inflammatory drugs (NSAIDs) are thought to reduce cancer risk by inhibiting cyclo-oxygenases, resulting in deceased formation of inflammatory mediators and oxidative stress. We examined whether the level of one oxidative stress marker, 15-F(2t)-isoprostane, was affected by NSAID use in plasma and breast nipple aspirate fluids (NAF) of pre-menopausal women who were participating in a dietary intervention trial (n=121). Baseline levels of 15-F(2t)-isoprostane were lower in NSAID users than non-users in both NAF and plasma, although the differences did not persist after intervention. Over the duration of the study, information on NSAID use was collected five times, and average 15-F(2t)-isoprostane levels in both NAF and plasma exhibited a statistically significant trend for decreases with increased frequency of NSAID use. These results indicate that NSAID use can result in lower levels of 15-F(2t)-isoprostane, which may have implications for the effects of NSAID use on breast cancer risk.