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Background and Aims: In the United States, little is known about the rates of interval upper gastrointestinal (GI) cancer (possibly missed out) after an esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported interval cancer rates of 7–26%. We aimed to study the rate and predictors of interval upper GI cancers in the United States. Methods: Using the random 5% sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients diagnosed with esophageal or gastric cancer during 2000–2007. EGD performed within 36 months prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6–36 months after EGD were defined as interval (vs. detected) cancers. The chi-square test and the multivariate logistic model were used in statistical analysis. Results: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were diagnosed with interval cancers 6–36 months after EGD. The rate of interval cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non-gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI 0.25–0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28–0.997) were associated with a lower likelihood of interval cancers. Sensitivity analyses limited to outpatient EGDs or interval cancers 6–30 months after EGDs led to similar results. Conclusions: The rate of interval cancers after EGD is the same as the rate of colonoscopy among Medicare patients in the United States. EGDs performed by gastroenterologists and in in-patient settings were associated with a lesser likelihood of interval cancers. [ABSTRACT FROM AUTHOR]