BACKGROUND & AIMS: Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations. METHODS: We performed a pooled analysis of 6 population-based studies within the Barrett’s and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model. RESULTS: Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56-0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66-1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (>/=10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43-0.73; P(trend) < .001) and 0.63 (95% CI, 0.45-0.90; P(trend) = .04), respectively. CONCLUSIONS: Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.