Objective This study aims to synthesize cost and health outcomes for current treatment pathways for esophageal adenocarcinoma and high-grade dysplasia (HGD) and to model comparative net clinical and economic benefits of alternative management scenarios. Methods A decision-analytic model of real-world practices for esophageal adenocarcinoma treatment by tumor stage was constructed and validated. The model synthesized treatment probabilities, survival, quality of life, and resource use extracted from epidemiological datasets, published literature, and expert opinion. Comparative analyses between current practice and five hypothetical scenarios for modified treatment were undertaken. Results Over 5 years, outcomes across T stage ranged from 4.06 quality-adjusted life-years and costs of $3,179 for HGD to 1.62 quality-adjusted life-years and costs of $50,226 for stage T4. Greater use of endoscopic mucosal resection for stage T1 and measures to reduce esophagectomy mortality to 0-3 % produced modest gains, whereas a 20 % reduction in the proportion of patients presenting at stage T3 produced large incremental net benefits of $4,971 (95 % interval, $1,560-8,368). Conclusion These findings support measures that promote earlier diagnosis, such as developing risk assessment processes or endoscopic surveillance of Barrett's esophagus. Incremental net monetary benefits for other strategies are relatively small in comparison to predicted gains from early detection strategies.