Abstract: Background: Acute appendicitis is one of the most frequent abdominal surgical emergencies. Intra-abdominal abscess is a frequent post-operative complication. The aim of this meta-analysis was to compare peritoneal irrigation and suction versus suction only when performing appendectomy for complicated appendicitis. Methods: According to PRISMA guidelines, a systematic review was conducted and registered into the Prospero register (CRD42020186848). The risk of bias was defined to be from low to moderate. Results: Seventeen studies (9 RCTs and 8 CCTs) were selected, including 5315 patients. There was no statistical significance in post-operative intra-abdominal abscess in open (RR 1.27, 95% CI 0.75–2.15; I2 = 74%) and laparoscopic group (RR 1.51, 95% CI 0.73–3.13; I2 = 83%). No statistical significance in reoperation rate in open (RR 1.27, 95% CI 0.04–2.49; I2 = 18%) and laparoscopic group (RR 1.42, 95% CI 0.64–2.49; I2 = 18%). In both open and laparoscopic groups, operative time was lower in the suction group (RR 7.13, 95% CI 3.14–11.12); no statistical significance was found for hospital stay (MD − 0.39, 95% CI − 1.07 to 0.30; I2 = 91%) and the rate of wound infection (MD 1.16, 95% CI 0.56–2.38; I2 = 71%). Conclusions: This systematic review has failed to demonstrate the statistical superiority of employing intra-operative peritoneal irrigation and suction over suction-only to reduce the rate of post-operative complications after appendectomy, but all the articles report clinical superiority in terms of post-operative abscess, wound infection and operative times in suction-only group.