Consumption of maté, a tea-like infusion of the herb Ilex paraguariensis, is common in South America. Drinkers have high risks of upper aerodigestive tract cancers, but it is conceivable that this high risk may be attributable to confounding by smoking alcohol, and other exposures. To test this hypothesis, we analyzed the data from a case-control study of upper aerodigestive tract cancers conducted in Southern Brazil. We matched noncancer controls (N = 756) to cases (N = 378) on the basis of age, sex, and period of admission. We estimated the effect of mateé consumption by conditional logistic regression with adjustment for smoking, alcohol, sociodemographics, and several dietary items, considered as confounders. The unadjusted relative risk (RR) for all upper aerodigestive tract cancers was 2.1 [95% confidence interval (CI) = 1.6-2.7]. Some excess risk persisted after adjustment for potential confounders (RR = 1.6; 95% CI = 1.2-2.2). Most of the excess risk for maté drinkers was for oral (RR = 1.9; 95% CI = 1.1-3.3) and laryngeal (RR = 2.2; 95% CI = 2.2; 95% CI = 1.1-4.5) cancers. There was no evidence of associations with coffee and tea drinking. We conclude that the association of maté consumption with upper aerodigestive tract cancer risk is unlikely to result from insufficient control of confounding by critical exposures. Owing to its high prevalence in Southern South America, maté drinking may be linked to as many as 20% of all cases occurring in this region.