Abstract Background: An association between red and processed meat and esophageal cancer (EC) and gastric cancer (GC) has been suggested. Northern Iran is one of the most burdened countries by these malignancies. This study aims to investigate the effect exerted by different meat types on both EC and GC, including their subtypes, in a high risk population. Methods: Golestan cohort study (GCS) is a population-based cohort of 50,045 individuals aged 40-75 years from northeast Iran. The participants were selected by random sampling of people without a history of upper-GI cancer. Detailed data on different exposures were collected upon enrolment using validated questionnaires, in particular a 116-item food frequency questionnaire was specifically designed and validated for this population and was used to assess dietary habits among the cohort. Total meat items included unprocessed red meat (lamb, beef, and hamburger), organ meat (liver, kidney and heart), processed meat (sausage and deli meat), white meat (chicken and fish). For the analysis, a term for total red meat intake was created including the first three types of meat. We considered quintiles of meat consumption, using grams and density (g/total kcal). The outcomes were EC, carcinoma of the lower third of the esophagus, esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EA), GC, cardia GC and non-cardia GC. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% CIs for the association between meat types and cancers. Results: The cohort reported a mean intake of 18.4 g/day (95% CI=17.8-18.6) for total red meat, and 72.1 g/day (95% CI=70.3-73.8) for white meat. These values correspond to an intake density of 8.11 g per 1000 kcal (95% CI=8.05-8.19) and 32.3 g (95% CI= 32.0-32.5) per 1000 kcal for total red and white meat respectively. Of 49,585 participants included in the analyses after 12 year mean follow-up, 369 developed EC, including 141 cases of the lower esophagus, 309 ESCC cases and 20 EAC, and 368 developed GC, of whom 216 cardia and 97 non-cardia. No association was found for EC except for red meat among women (HR 1.13, 95% CI 1.00-1.27 for one-quintile increase in intake). The risk of GC was increased for total red meat (HR 1.08, 95% CI 1.00-1.17) and red meat intake separately (HR 1.09, 95% CI 1.00-1.18). These trends were stronger among men, non-cardia GC, and red meat (HR 1.23, 95% CI=1.02-1.48). Cooking type did not influence the risk of developing any cancer, while we observed strong associations between red meat unprocessed and overall and GC among opium users, suggesting an effect modification. Conclusions: Red meat intake is associated to GC, but not EC. Other types of meat show no relation. Lifestyle habits such as opium use can increase this risk of GC in high meat consumers. Citation Format: Giulia Collatuzzo, Arash Etemadi, Farin Kamangar, Abnet Christian, Sandy Dawsey, Paul Brennan, Masoud Sotoudeh, Hossein Poutschi, Masoud Khoshnia, Akram Pourshams, Reza Malekzadeh, Paolo Boffetta. Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 729.