Objective <p>To describe the short-term treatment outcomes and intermediate-term appendectomy rates following protocol-based medical treatment in carefully selected patients with uncomplicated acute appendicitis without appendicolith.</p> Methods <p>This single-arm retrospective cohort study was conducted at a single tertiary center. Patients with uncomplicated acute appendicitis without appendicolith on computed tomography (CT) were treated following a standardized protocol consisting of intravenous antibiotics, a 48-hour in-hospital observation period, and systematic follow-up. The primary outcome was treatment success during initial hospitalization, defined as symptom resolution and discharge without the need for appendectomy. Secondary outcomes included appendectomy rates and complications during the follow-up period.</p> Results <p>Sixty-eight patients received protocol-based medical treatment. All 68 patients (100%) completed initial hospitalization successfully without requiring appendectomy. During a median follow-up of 2.8 years, six patients (8.8%) underwent appendectomy; however, only one of these (1.5%) represented true symptomatic recurrence, while the remaining five (7.4%) underwent surgery for non-clinical reasons including patient preference, anxiety, and pregnancy-related concerns. No major complications were observed among patients managed with antibiotics.</p> Conclusion <p>Protocol-based medical treatment achieved complete short-term treatment success in this selected cohort of patients with uncomplicated acute appendicitis without appendicolith. The overall appendectomy rate during follow-up remained low, with true symptomatic recurrence observed in only one patient. These findings, while limited by the single-arm observational design and small sample size, supported the feasibility of this approach when combined with reliable imaging assessment, systematic patient selection, and structured follow-up.</p>