Purpose: To compare the outcome of initially nonoperative treatment with immediate appendectomy for simple appendicitis in children. Methods: Between September 2012 and June 2014 children aged 7–17 years with a radiologically confirmed simple appendicitis were invited to participate in a multicentre prospective cohort study in which they were treated with an initially nonoperative treatment strategy; nonparticipants underwent immediate appendectomy. In October 2015, their rates of complications and subsequent appendectomies, and health-related quality of life (HRQOL) were assessed. Results: In this period, 25 children were treated with an initially nonoperative treatment strategy and 19 with immediate appendectomy; median (range) follow-up was 25 (16–36) and 26 (17–34) months, respectively. The percentage [95%CI] of patients experiencing complications in the initially nonoperative group and the immediate appendectomy group was 12 [4–30]% and 11 [3–31]%, respectively. In total 6/25 children (24%) underwent an appendectomy; none of the 6 patients operated subsequently experienced any postappendectomy complications. Overall, HRQOL in the nonoperative treatment group was similar to that of healthy peers. Conclusions: Outcome of initially nonoperative treatment for acute simple appendicitis in children is similar to the outcome in those who undergo immediate appendectomy. Initially nonoperative management seems to be able to avoid appendectomy in 3 out of 4 children. Level of evidence: 2 (prospective comparative study). This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.