Background Our study aimed to compare the clinical outcomes and cost-efficiency of antibiotic management versus laparoscopic appendectomy for acute uncomplicated appendicitis (AUA) in children during the COVID-19 pandemic when resources were limited and transmission risks uncertain. Method In this prospective case-control study between Apr 2020 to Jan 2022, we analyzed the data of 139 children diagnosed with AUA meeting the following inclusion criteria: symptoms duration of ≤48 hours, appendix diameter ≤11 mm and no appendicolith. 78/139 cases were treated with antibiotics while 61 matched controls underwent upfront laparoscopic appendectomy. Antibiotic regimes were intravenous Ceftriaxone/Metronidazole or Amoxicillin/Clavulanic acid for 48 hours, followed by oral antibiotics to complete total 10-days course. Results 8/78 (10.3%) children had early failure (within 48hours) requiring appendectomy. 17/78 patients (21.8%) experienced late recurrence within mean follow-up time of 16.2±4.7 months. There were no statistical differences in peri-operative complications, negative appendicectomy rate, incidence of perforation and hospitalization duration between antibiotic and surgical treatment groups. Cost per patient in upfront surgical group was significantly higher ($6208.5±5284.0) than antibiotic group ($3588.6±3829.8; p = 0.001). Conclusion Despite 21.9% risk of recurrence of appendicitis in 16.2±4.7 months, antibiotic therapy for AUA appears to be a safe and cost-effective alternative to upfront appendectomy.