This study prospectively investigated the association between physical activity and esophageal and gastric carcinoma in a cohort of 487,732 U.S. men and women, followed from 1995/96 to December 31, 2003. Physical activity was associated with reduced risk of esophageal and gastric adenocarcinomas but was unrelated to esophageal squamous cell carcinoma. Physical activity may play a role in the prevention of upper gastrointestinal tract adenocarcinomas. No association was seen between physical activity and esophageal squamous cell carcinoma.