Participants in the General Population Trial, a randomized nutrition intervention trial in Linxian, China, who received a combination of selenium, beta-carotene, and vitamin E supplements, had statistically significantly lower cancer mortality rates than those who did not receive the supplements. In the current study, we used a case-cohort design to examine the association between pre-trial serum vitamin E levels and the risks of developing esophageal and gastric cancers during the trial. We measured serum alpha- and gamma-tocopherol and cholesterol levels in 1072 case patients with incident esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), or gastric noncardia cancer (GNCC) and in 1053 control subjects. The relative risks for comparisons of the highest to the lowest quartiles of serum alpha-tocopherol were 0.63 (95% confidence interval [CI] = 0.44 to 0.91) for ESCC, 0.84 (95% CI = 0.55 to 1.26) for GCC, and 2.05 (95% CI = 0.89 to 4.75) for GNCC. Serum gamma-tocopherol level was not associated with the incidence of any of these cancers. Our findings provide support for the role of alpha-tocopherol in the etiology of upper gastrointestinal cancers.