Objective To reduce the incidence of cholangitis related with percutaneous transhepatic biliary drainage (PTBD) by comparing wire-guided PTBD with conventional PTBD . Methods A total of 174 consecutive patients with biliary disease who underwent biliary drainage in our hospital from January 2011 to December 2017 were enrolled in this retrospective study. There were 85 patients undergoing conventional PTBD (conventional group), and 89 wire-guided PTBD ( wire-guide group). In the wire-guided group, the contrast media was not injected immediately after puncture, on the contrary, the needle coat was inserted deeply along the bile duct thereafter, then the bile was extracted to reduce the pressure of bile duct, at last the contrast media was infused. The successful drainage rate and incidence of cholangitis related with PTBD were compared between the two groups. Results The advantage of the wire-guided group was significant in reducing the incidence of cholangitis compared with the conventional group [10.1% (9/89) VS 21.2% (18/85), 2=5.270, P=0.022], although the successful drainage rate was not significantly different between the two groups [94.4% (84/89) VS 97.6% (83/85), 2=1.200, P=0.273]. Conclusion Wire-guided PTBD may yield a similar success rate, but can reduce the incidence of cholangitis compared with conventional PTBD.