||OBJECTIVES: Red and processed meats could increase cancer risk through several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied. METHODS: We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During ∼10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas. RESULTS: Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile=1.79, 95% CI: 1.07-3.01, P for trend=0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR=1.44, 95% CI: 1.01-2.07, P for trend=0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR=1.35, 95% CI: 0.97-1.89, P for trend=0.022; HR=1.45, 95% CI: 0.99-2.12, P for trend=0.463; or HR=1.47, 95% CI: 0.99-2.20, P for trend=0.063, respectively). Benzo[a]pyrene, nitrate, and nitrite were not associated with esophageal or gastric cancer. CONCLUSIONS: We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer.