OBJECTIVE：To overview the systematic review on the effectiveness of indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis （PEP），and to provide reliable evidence-based reference for the prevention of PEP. METHODS ：Retrieved from PubMed ，the Cochrane Library ，Embase，CBM，CNKI，Wanfang database and VIP，systematic review on indomethacin in the prevention of PEP were collected during the inception to Nov. 2020. The methodological quality ，report quality and evidence quality of the included studies were evaluated by AMSTAR 2 scale，PRISMA statement and GRADE method. The effectiveness of PEP prevention was described. RESULTS ：Finally，23 systematic reviews were obtained ，including 12 in Chinese and 11 in English. Tweenty-two systematic reviews showed that compared with placebo ， indomethacin could effectively reduce the incidence of PEP. Eight systematic reviews showed that indomethacin significantly reduced the incidence of moderate and severe PEP compared with placebo. Five systematic reviews showed that indomethacin could reduce the incidence of postoperative hyperamylasemia compared with placebo. Three systematic reviews showed that indomethacin also had a good preventive effect on people with high risk of PEP. PRISMA score of included systematic reviews ranged from 15 to 25. The quality evaluation of AMSTAR 2 methodology included in systematic reviews was low ，and the key items of complete report were 4，9，11 and 13. The GRADE evidence quality evaluation of the included systematic reviews showed that the quality of the evidence was concentrated in the low level. CONCLUSIONS ：Indomethacin has a certain effect in the prevention of PEP ，but the overall evidence quality of the included literatures is generally not high. It needs to be further validated by high-quality clinical research.