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Esophageal capsule endoscopy (ECE) is a promising new technology for the detection of esophageal pathology. Potential advantages for Barrett’s esophagus (BE) screening include ability to return to work as a result of lack of intravenous sedation.We designed a Markov model to compare lifetime costs and life expectancy for a cohort of 50-year old men with chronic GERD for the presence of BE. We compared the base-case strategy of no screening for BE to 2 competing screening strategies: (1) ECE followed by upper endoscopy (EGD) if BE were suspected or if there was poor visualization on the ECE; and (2) standard sedated EGD with biopsy. Cost estimates were obtained from a third-party payer perspective. For each strategy we determined lifetime costs, life-years gained, numbers of esophageal cancers detected, death rates from esophageal cancer, and procedural deaths.Initial EGD was more expensive but more effective compared with the no screening strategy. Assuming a theoretical cohort of 10,000 patients with GERD, initial EGD cost $1988 and was associated with 18.54 life-years compared with $2392 and 18.36 life-years for the ECE arm and $901 and 18.30 life-years for the no screening arm. The incremental cost-effectiveness ratio of screening with EGD compared with the no screening arm was $4530 per life-year gained. The model was robust to a wide range of sensitivity analyses.Initial EGD appears more effective and less costly compared with ECE under base-case conditions for patients with chronic GERD undergoing screening for BE.