Objective: To compare the success rates of wire-guided biliary cannulation (WGC) and conventional cannulation (CC) and their effect on the outcome of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods: All randomized controlled trials (RCTs) were collected by searching CNKI, WanFang Data, CBM, PubMed, Embase and Cochrane Library.The assessment of methodological quality and data extraction of the included studies were performed independently by two reviewers. Meta-analysis was conducted with RevMan 5.2 software. Results: Ten RCTs, with a total of 3 262 patients enrolled, were retrieved.Meta-analysis demonstrated that WGC had a higher success rate(RR=1.04, 95%CI 1.01-1.06, P<0.01)and a lower risk of PEP after cannulation (RR=0.54, 95%CI 0.41-0.71, P<0.01). The main reason for the lower risk of PEP was due to lower proportion of mild PEP patients after WGC(RR=0.52, 95%CI 0.36-0.73, P<0.01), while the incidence of modest and severe PEP was comparable in the two groups(modest group: RR=0.84, 95%CI 0.43-1.64, P=0.61; severe group: RR=0.53, 95%CI 0.22-1.31, P=0.17). Conclusion: WGC may increase the success rate of cannulation and reduce the incidence of PEP because of less complications of mild PEP.