Objective To compare the efficacy of endoscopic retrograde appendicitis therapy (ERAT) and sub-endoscopic retrograde appendicitis therapy (SERAT) for the treatment of acute appendicitis. Methods The retrospective study was performed on consecutive patients who underwent SERAT (21 cases) and ERAT (30 cases) for acute appendicitis in Shandong Provincial Third Hospital from November 2021 to April 2023. Patient baseline information, clinical treatment, hospitalization costs, and hospital stay were analyzed, and complications and recurrence were followed up. Results There was no significant difference between the two groups regarding age, gender, clinical manifestation, laboratory and imaging data, or Alvrrado score (P>0.05). Compared with the ERAT group, the operation time was shorter in the SERAT group (23.6±10.1 min VS 44.8±18.8 min, t=4.679, P<0.001). There were no significant differences between the two groups in stent implantation rate [61.9% (13/21) VS 70.0% (21/30), χ2=0.364, P=0.546], fecalith removal rate [38.1% (8/21) VS 33.3% (10/30), χ2=0.123, P=0.726], postoperative time for temperature (19, 2, 0 and 26, 3, 1 cases after 0 to 1 day, >1 to 3 days and >3 days, respectively, χ2=0.723, P=0.697) and white blood cell count normalization (20, 1, 0 and 27, 2, 1 cases after 0 to 1 day, >1 to 3 days and >3 days, respectively,χ2=0.813, P=0.666), proportion of visual analogue scale scores<3 at 6 hours after treatment [100.0% (21/21) VS 90.0% (27/30), χ2=2.231, P=0.135], length of hospital stay (3.4±1.2 days VS 4.5±2.9 days, t=1.579, P=0.121), hospitalization cost (15 393.0±4 352.5 yuan VS 17 836.0±5 134.6 yuan, t=1.777, P=0.082), or incidence of complications [0.0% (0/21) VS 0.0% (0/30), χ2=0.000, P=1.000]. The recurrence rate in SERAT group (0.0%, 0/21) was significantly lower than that in ERAT group (23.3%, 7/30) (P=0.017). Conclusion SERAT is a safe and effective minimally invasive approach for managing acute appendicitis, characterized by a shorter operation duration and a lower recurrence rate compared to ERAT.