Abstract Background. Head and neck cancer (HNC) is a significant cause of morbidity and mortality, with over half a million cases worldwide each year. While high fruit and vegetable intake is thought to be protective against HNC, it is unclear whether vitamin and mineral supplement intake is associated with decreased risk of these malignancies. Previous case-control studies in the US have suggested vitamin E supplement intake is inversely associated with oral cavity and pharyngeal cancers. In a large randomized controlled trial, supplementation with alpha-tocopheryl acetate and/or beta-carotene was not associated with upper aerodigestive tract cancer incidence; however an inverse association was suggested for early stage laryngeal cancers. Methods. We analyzed individual-level pooled data from 12 case-control studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. There were a total of 2,028 oral cavity cancer cases, 2,465 pharyngeal cancer cases, and 874 laryngeal cancer cases. Odds ratios (OR) and 95% confidence intervals (CIs) for ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta carotene, iron, selenium, and zinc supplement were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. Results. A decreased risk of HNC was observed with ever use of vitamin C (OR=0.76, 95%CI=0.59-0.96) and with ever use of calcium supplements (OR=0.64, 95%CI=0.42-0.97). There did not appear to be any associations between HNC risk and ever use of any vitamins (OR=0.87, 95%CI=0.71-1.06), multiple vitamins (OR=0.99, 95%CI=0.82-1.19), vitamin A (OR=1.04, 95%CI=0.54-1.98), vitamin E (OR=0.71, 95%CI=0.45-1.11), beta-carotene (OR=1.35, 95%CI=0.65-2.81), iron (OR=0.79, 95%CI=0.54-1.16), selenium (OR=1.21, 95%CI=0.35-4.22) or zinc (OR=0.88, 95%CI=0.34-2.26). Dose-response trends were suggested for years of use of vitamin C (p for trend=0.03) and calcium (p<0.01) with decreasing HNC risk, but not for other vitamin or mineral supplement use. Increased cumulative calcium intake (in tablets) was also associated with decreasing HNC risk (p for trend<0.01). Differences by cancer subsite (oral cavity, pharynx, larynx) were not observed. Conclusions. This is the first time that inverse associations were observed for HNC risk with both vitamin C use and with calcium use in an extremely large sample size. The next steps for our pooled analyses will include adjustment on micronutrients from dietary intake and stratification on HPV infection status where possible. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2818.