Background <p>Upper gastrointestinal (GI) disorders represent a major cause of morbidity worldwide, and esophagogastroduodenoscopy (EGD) remains the gold standard for both diagnosis and therapeutic guidance. In resource-limited settings such as the Gaza Strip, the utilization of EGD provides critical insights into disease burden, patient characteristics, and clinical outcomes. This study aimed to evaluate the demographic characteristics, clinical indications, endoscopic findings, and management outcomes of patients undergoing EGD at the Gaza Strip Hospitals.</p> Methods <p>A retrospective analytical study was conducted at the endoscopy unit of the Gaza Strip Hospitals, covering the period from 2017 to 2022. All patients who underwent EGD during this timeframe were included, while those with combined double-scope procedures, colonoscopy alone, or procedures performed before 2017 were excluded. Data were extracted from hospital records using a structured questionnaire developed based on recent literature. Variables included sociodemographic characteristics, presenting complaints, laboratory investigations, and endoscopic findings. Data were analyzed using SPSS version 23.</p> Results <p>A total of 1,159 patients were included, with a mean age of 42.6 ± 16.8 years (range 2–92 years), and a nearly equal sex distribution (50.6% male vs. 49.4% female). The majority of patients were admitted through the outpatient department (92.3%). The most frequent presenting complaint was epigastric pain (56.3%), followed by gastroesophageal reflux disease (8.3%). Most procedures were performed under local anesthesia (72.4%), predominantly with midazolam. EGD findings revealed normal esophagus in 84.6% of patients, while 38.6% had incompetent cardia without hiatus hernia and 26.2% with hiatus hernia. Hyperemic gastric mucosa was the most common stomach finding (57.1%), while 83.7% of patients had hyperemic antral mucosa. Duodenal evaluation showed normal first part of duodenum (D1) in 85.4% and normal second part of duodenum (D2) in 96.9% of patients. The most frequent overall diagnostic conclusion was diffuse gastritis (29.4%), while mass lesions were identified in 2.3% of cases.</p> Conclusion <p>EGD in the Gaza Strip revealed a high prevalence of gastritis and reflux-related disorders, with a smaller but clinically significant proportion of structural abnormalities and mass lesions. Epigastric pain was the leading indication for the procedure. These findings highlight the continued importance of EGD as a diagnostic tool in resource-constrained healthcare systems and emphasize the need for preventive measures, particularly for gastritis and reflux disease. Further prospective studies are recommended to evaluate risk factors, treatment adherence, and long-term outcomes.</p>