A retrospective hospital-based case-control study was carried out at the Oncology Institute of Montevideo, Uruguay, to investigate the role of maté consumption in esophageal cancer risk. The study included 344 cases with squamous cell carcinoma of the esophagus and 469 controls recruited between January 1988 and August 2000. Maté consumption was significantly associated with an increased risk of developing esophageal cancer and showed a clear dose response, with a relative risk of 2.84 [95% confidence interval (CI), 1.41-5.73] for those drinking more than 1 liter/day of maté as compared with nondrinkers. Subjects who self-reported drinking maté at a very hot temperature had an almost 2-fold increase in risk [odds ratio (OR), 1.87; 95% CI, 1.17-3.00] compared with those drinking warm to hot maté, after adjusting for cumulative consumption of maté. Maté amount and temperature were observed to have independent effects and, although no departure from multiplicativity was observed between the two covariates, those drinking more than 1 liter/day of maté at a very hot temperature had a 3-fold increase in risk (OR, 2.95; 95% CI, 1.30-6.74) compared with those drinking less than 0.5 liter/day of maté at a warm to hot temperature. Subjects with high cumulative exposure to maté in the presence of low alcohol and tobacco exposures presented a lower-risk estimate (OR, 1.52; 95% CI, 0.88-2.62), whereas those with high cumulative exposures to maté, alcohol, and tobacco presented a 7-fold increase in esophageal cancer risk (OR, 7.10; 95% CI, 3.75-13.46). The population-attributable fraction as a result of maté consumption was calculated to be 53%, of which the sole effect of amount and temperature was 14.8 and 12.6% respectively, and 14.9% was attributable to high maté consumption at high temperature.