Background and Objectives: Acute appendicitis is the most common surgical emergency in children. The standard of care has been appendectomy for many years. However, in recent years, studies investigating antibiotic therapy alone have increased rapidly, suggesting that non-operative management may be an effective alternative with a lower risk of complications. In this study, we compared two antibiotic regimens (ceftazidime/metronidazole and ampicillin/metronidazole) to evaluate the effectiveness of two antibacterial strategies. Materials and Methods: A total of 41 children aged 7–18 years were enrolled and randomly assigned to one of the two treatment groups, with the follow-up conducted over one year to assess recurrence. For the evaluation of antibiotic effectiveness, inflammation was assessed using leukocyte count, C-reactive protein, and the biomarkers IL-6, IL-8, and MCP-1, which were measured on each of the three days of inpatient antibiotic therapy. Results: Analysis of the collected data revealed no statistically significant difference in inflammatory markers between the two treatment groups. Conclusions: These findings suggest that both antibiotic regimens offer comparable clinical outcomes and may be used interchangeably in clinical practice.