Acute gastroenteritis (AGE) is a gastrointestinal tract disease often caused by consuming food or water contaminated by bacteria, viruses, or parasites, that can lead to severe symptoms requiring hospitalization. A retrospective study on patients admitted for AGE between 2021 and 2023 at the Pediatrics and Infectious Diseases Departments of Lecce Hospital was conducted. Demographic characteristics, year and month of admission, length of hospital stay, etiological agents, co-infections, and blood chemistry data of patients were collected. The study included 103 patients ranging in age from 0 to 15 years, with 58.25% being male. A total of 78 bacterial, 35 viral, and 7 parasitic infections were identified. The most commonly detected pathogens were (38.83%), Norovirus (28.16%), (22.33%), and (10.68%). Only a few cases of (5.83%) were identified. Additionally, 17 co-infections (16.50%) were detected. Viral infections are the primary cause of hospitalization for AGE in children <5 years, while bacterial infections are more common among older patients. The significantly higher number of children <5 years old with elevated creatinine compared to children ≥5 years suggested that young children are more susceptible to dehydration than older children. Few cases of AGE were attributed to pathogens for which a vaccine has already been licensed. AGE is a serious health concern that could be effectively prevented by implementing food-based and community-level sanitation systems, as well as by increasing vaccination coverage of available vaccines and developing new effective and safe vaccines.