The association between long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) and non-Hodgkin lymphoma (NHL) was examined using data collected between October 2001 and May 2004 in an ongoing population-based case-control study in the San Francisco Bay Area. NHL cases were identified using rapid case ascertainment and Surveillance, Epidemiology, and End Results registry data. Control participants were frequency-matched to cases by age, sex, and county of residence. Participants completed in-person interviews designed to measure potential NHL risk factors. Questions were asked regarding use during the past 20 years of aspirin, prescription and over-the-counter nonselective NSAIDs, and cyclooxygenase-2 (COX-2) inhibitors. A total of 1,000 cases and 1,060 controls contributed data for these interim analyses. Analyses were carried out for men and women and for both sexes combined. After adjustment for age and sex, there was no consistent association between long-term use and NHL for all NSAIDs combined, aspirin, nonselective NSAIDs, and COX-2 inhibitors. For women, long-term aspirin use may be associated with a decreased risk of NHL (for 3-<9 years of use, odds ratio=0.41, 95% confidence interval: 0.18, 0.94). Conversely, although the confidence intervals were wide, the adjusted odds ratios for COX-2 inhibitor use were nearly twofold for women, indicating a possible increase in NHL risk associated with regular use of COX-2 inhibitors.