Objective To investigate the efficacy and safety of endoscopic appendix intubation and irrigation (EAI) on acute uncomplicated appendicitis. Methods This prospective non-randomized study examined 169 patients with suspected acute uncomplicated appendicitis at The First Affiliated Hospital of Fujian Medical University from October 2015 to 2017. Patients were divided into three groups: endoscopic appendix intubation and irrigation (EAI, n  = 18), laparoscopic appendectomy (LA, n  = 87), and antibiotic alone (A, n  = 64). The treatment success rate, duration of hospitalization, medical costs, operation time, duration of abdominal pain, fasting time, complications, and recurrence were analyzed. Results The three groups had no significant differences in baseline characteristics (age, gender, Alvarado score, white blood cell count, and neutrophil count; all P  > 0.05). Compared to the LA group, the EAI group had shorter durations of the operation, fasting, and abdominal pain; less use of oral and intravenous antibiotics; and lower medical costs (all P  < 0.05). Compared to the A group, the EAI group had shorter durations of abdominal pain and hospitalization, and less use of intravenous antibiotics (all P  < 0.05). The EAI group had no complications, but 3 patients (3.4%) in the LA group had surgery-related complications. Conclusion EAI is a safe and effective treatment for acute uncomplicated appendicitis. Patients who received EAI had shorter durations of abdominal pain and hospitalization than those who received LA or conservative antibiotic treatment. Trial registration number and agency ChiCTR-IPN-15006565, Chinese Clinical Trial Registry