Background:Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.Methods:Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.Results:Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.Conclusion:Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.British Journal of Cancer advance online publication 28 February 2013; doi:10.1038/bjc.2013.73 www.bjcancer.com.