Objective To compare adverse events (AEs) of regional citrate anticoagulation (RCA) versus heparin anticoagulation during continuous renal replacement therapy (CRRT) through systematic review and trial sequential analysis. Methods Based upon the relevant randomized control trials (RCT) comparing RCA and heparin anticoagulation during CRRT in both domestic and foreign databases, the authors re-analyzed various AEs including at least one of the following episodes: hypocalcemia, metabolic acidosis, metabolic alkalosis, hemorrhage and heparin-induced thrombocytopenia (HIT). Meta-analysis was performed with Revman 5.2 and TSA 0.9 software for trial sequential analysis (TSA). Results Among a total of 791 items, 18 articles were included. As compared with heparin, RCA lowered the frequency of overall AEs (RR=0.54, 95%CI:0.35-0.82, P=0.004). And hemorrhagic risk dropped by 73% (RR=0.27, 95%CI:0.19-0.38, P