OBJECTIVES: The most common technique used to achieve primary deep biliary cannulation is the standard contrast-assisted method. To increase the success rate and reduce the risk of complications, a wire-guided cannulation strategy has been proposed. Prospective studies provided conflicting results as to whether the wire-guided cannulation technique increases the cannulation rate and reduces post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis risk compared with the standard method. The objective of this study was to carry out a meta-analysis of randomized controlled trials (RCTs) that compares primary biliary cannulation and post-ERCP pancreatitis rates with the wire-guided method and the standard cannulation technique. METHODS: Literature searches of electronic databases and online clinical trial registers up to March 2009 were conducted to identify RCTs comparing primary cannulation and post-ERCP pancreatitis rates with the wire-guided method and the standard cannulation technique. A meta-analysis of these clinical trials was performed. RESULTS: Five RCTs were included. Overall, the primary cannulation rates reported with the wire-guided cannulation technique and the standard method were 85.3 and 74.9%, respectively. The pooled analysis of all the selected studies comparing the wire-guided cannulation technique with the standard method yielded an odds ratio (OR) of 2.05 (95% confidence interval (CI): 1.27-3.31). The pooled analysis comparing the post-ERCP pancreatitis rates for the wire-guided-cannulation groups with those for the standard-method groups yielded an OR of 0.23 (95% CI: 0.13-0.41). CONCLUSIONS: This meta-analysis shows that the wire-guided technique increases the primary cannulation rate and reduces the risk of post-ERCP pancreatitis compared with the standard contrast-injection method. Further large, well-performed, randomized controlled studies are needed to confirm these findings.