Background: Surgery is the clinically preferred treatment for high perianal abscesses. Incision and seton drainage improve the cure rate and reduce recurrence. We aimed to systematically evaluate the clinical effect and safety of incision and seton drainage in the treatment of high perianal abscess. Methods: China Knowledge Network (CNKI), WanFang database, VIP database, PubMed, and Cochrane Library were searched and all relevant Chinese and English language documents until July 2021were retrieved. All records that described randomized clinical trials (RCTs) of incision and seton drainage for the treatment of high perianal abscess were eligible. Documents that met the inclusion criteria were evaluated for bias using the Cochrane Collaboration Risk Evaluation Standard, and Revman5.4 software was used to analyze the data. Results: Fourteen RCTs were included. The results of nine studies showed that the clinical cure rate of the incision-seton group was higher than that of the incision-drainage group (P<0.05). Seven studies showed that the wound healing time of the incision-seton group was shorter than that of the incision-drainage group (P<0.05). Four studies showed that the visual analogue scale (VAS) score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Five studies showed that the Wexner score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Six studies showed that the formation rate of anal fistula in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Six studies demonstrated that the recurrence rate of abscess in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Seven studies showed that the incidence of adverse events in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Five studies demonstrated that the length of stay in the incision-seton group was shorter than that of the incision drainage group (P<0.05). Discussion: The choice of surgical methods in clinical research has always been controversial. The incision-seton method can effectively and safely treat high perianal abscess. However, the results of this meta-analysis still leave some gaps in the evidence. More large-sample, high-quality, and multi-center RCTs are needed.