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Background: Esophagogastroduodenoscopy (EGD) is a valuable tool for diagnosing and treating upper gastrointestinal disease. Prioritizing the use of EGD in resource-limited settings must be customized to local populations to maximize population benefit from the examination., Methods: Cross-sectional, retrospective review of EGD reports was conducted at Kamuzu Central Hospital (KCH), Lilongwe, Malawi. Esophageal tumors were defined as obstructive or nonobstructive and esophageal varices were graded on a scale of I to IV. Descriptive statistics were calculated and logistic regression performed for each disease state compared with all other reports., Results: A total of 1,034 cases were reviewed (56% male; mean age (standard deviation), 44 (17) years). The most common indications were dysphagia (37%), hematemesis (21%), and epigastric pain (16%). The most common diagnoses were normal (36%), esophageal cancer (27%), and esophageal varices (17%). Eighty-six percent of esophageal tumors were obstructive and 45% of esophageal varices were grade III or IV. Normal examinations were more likely to be female, younger, and present with dyspepsia. Esophageal cancers were more likely to be male, older, present with dysphagia, and present from districts outside Lilongwe. Esophageal varices were more likely to present with hematemesis., Conclusions: EGD is a limited resource at KCH; patient selection should be guided by patient age and indication. The high burden of esophageal cancer and varices in Malawi suggests that therapeutic endoscopy would be beneficial.