African Americans have the highest colon cancer incidence and mortality rates among all US ethnic groups. Epidemiologic studies suggest that use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a reduced risk of colon cancer, but no study to date with adequate sample size has reported on the association among African Americans. The authors examined the association between NSAID use and risk of colon cancer in a population-based, case-control study in North Carolina that enrolled 731 African-American (294 cases, 437 controls) and 960 White (349 cases, 611 controls) participants between 1996 and 2000. Odds ratios were calculated using unconditional logistic regression for categories of NSAIDs and colon cancer risk. Inverse associations between regular NSAID use and colon cancer were similar for African Americans (odds ratio = 0.41, 95% confidence interval: 0.22, 0.77) and Whites (odds ratio = 0.48, 95% confidence interval: 0.28, 0.83) but stronger for women than men. Inverse associations were slightly weaker for occasional versus regular NSAID use, but they were similar for aspirin and nonaspirin NSAID use. These results add new knowledge suggesting that the protective effect of NSAIDs against colon cancer is similar among African Americans and Whites.