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Abstract Background Egypt faces a significant public health burden due to chronic liver diseases (CLD) and peptic ulcer disease. CLD, primarily caused by Hepatitis C virus (HCV) infection, affects over 2.9% of the population nationwide, with regional variations. Steatotic liver disease is rapidly emerging as a significant contributor to CLD, especially in urban areas. Acid-related disorders are another widespread condition that can significantly impact the quality of life. These factors and others significantly influence the indications and findings of gastrointestinal endoscopic procedures performed in Egypt. Aim We aimed to evaluate the clinico-demographic data, indications, and endoscopic findings in Egyptian patients undergoing gastrointestinal endoscopic procedures in various regions of Egypt. Methods This study employed a retrospective multicenter cross-sectional design. Data was collected from patients referred for gastrointestinal endoscopy across 15 tertiary gastrointestinal endoscopy units in various governorates throughout Egypt. Results 5910 patients aged 38–63 were enrolled in the study; 75% underwent esophagogastroduodenoscopy (EGD), while 25% underwent a colonoscopy. In all studied patients, the most frequent indications for EGD were dyspepsia (19.5%), followed by hematemesis (19.06%), and melena (17.07%). The final EGD diagnoses for the recruited patients were portal hypertension-related sequelae (60.3%), followed by acid-related diseases (55%), while 10.44% of patients had a normally apparent endoscopy. Male gender, old age, and the presence of chronic liver diseases were more common in patients from upper than lower Egypt governorates. Hematochezia (38.11%) was the most reported indication for colonoscopy, followed by anemia of unknown origin (25.11%). IBD and hemorrhoids (22.34% and 21.86%, respectively) were the most prevalent diagnoses among studied patients, while normal colonoscopy findings were encountered in 18.21% of them. Conclusion This is the largest study describing the situation of endoscopic procedures in Egypt. our study highlights the significant impact of regional variations in disease burden on the utilization and outcomes of GI endoscopy in Egypt. The high prevalence of chronic liver disease is reflected in the EGD findings, while the colonoscopy results suggest a potential need for increased awareness of colorectal diseases.