Background: Historically, appendectomy has been the treatment of choice for children with acute appendicitis. Nevertheless, there is growing interest in the effectiveness and security of non-invasive methods. This study aimed to comparing a non-operative therapy approach to appendectomy in children with simple acute appendicitis in terms of efficacy, safety, and cost-effectiveness. Methods: This prospective randomized controlled clinical experiment was undertaken at Benha University Hospital from December 2022 to December 2023. The study comprised children between the ages of 4 and 16 who had uncomplicated acute appendicitis pediatric Appendicitis Score (PAS 4 to 6). Appendectomy and non-operative (antibiotic therapy) patient groups were established. Extensive examinations were conducted, encompassing clinical, laboratory, and radiographic studies. Results: 120 patients out of a total of 133 were studied (60 in each group). Significant variations were noted in PAS, laboratory tests, days of hospitalization, and problems prior to release across the groups. Conclusion: Significant disparities in outcomes between non-operative and appendectomy treatments in pediatric patients with uncomplicated acute appendicitis are suggested by the study. Non-operative therapy has exhibited potential advantages in some instances, including decreased hospitalization and equivalent safety results.