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The operative treatment combined with preoperative biliary drainage (PBD) has been established as a safe Klatskin tumor (KT) treatment strategy. However, there has always been a dispute for the preferred technique for PBD technique. This meta-analysis was conducted to compare the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis between percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD), to identify the best technique in the management of KT.PubMed, EMBASE, and Web of Science were searched systematically for prospective or retrospective studies reporting the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis in patients with KT. A meta-analysis was performed, using the fixed or random-effect model, with Review Manager 5.3.PTBD was associated with lower risk of cholangitis (risk ratio [RR] = 0.49, 95% confidence interval [CI]: 0.36–0.67; P < .00001), particularly in patients with Bismuth-Corlette type II, III, IV KT (RR = 0.50, 95% CI: 0.33–0.77; P = .05). Compared with EBD, PTBD was also associated with a lower risk of pancreatitis (RR = 0.35, 95% CI: 0.17–0.69; P = 0.003) and with higher successful rates of palliative relief of cholestasis (RR = 1.20, 95% CI: 1.10–1.31; P < .0001). The incidence of hemorrhage was similar in these 2 groups (RR 1.29, 95% CI: 0.51–3.27; P = .59). The risk of biliary drainage-related cholangitis (RR = 1.96, 95% CI: 0.96–4.01; P = .06) and pancreatitis (RR = 1.62, 95% CI: 0.76–3.47; P = .21) was similar between endoscopic nasobiliary drainage groups and biliary stenting.In patients with type II or type III or IV KT who need to have PBD, PTBD should be performed as an initial method of biliary drainage in terms of reducing the incidence of procedure related cholangitis, pancreatitis, and improving the rates of palliative relief of cholestasis. Well-conducted randomized controlled trials with a universial criterion for PBD are required to confirm these findings.