Abstract Biliary drainage for Perihilar Cholangiocarcinoma (PCCA) can be performed either by endoscopic retrograde cholangiopancreatography or Percutaneous Transhepatic Biliary Drainage (PTBD). To date there is no consensus about which method is preferred. Taking that into account, the aim of this study is to compare Endoscopic Biliary Drainage (EBD) versus percutaneous transhepatic biliary drainage in patients with perihilar cholangiocarcinoma through a systematic review and metanalysis. A comprehensive search of multiple electronic databases was performed. Evaluated outcomes included technical success, clinical success, post drainage complications (cholangitis, pancreatitis, bleeding, and major complications), crossover, hospital length stay, and seeding metastases. Data extracted from the studies were used to calculate Mean Differences (MD). Seventeen studies were included, with a total of 2284 patients (EBD = 1239, PTBD = 1045). Considering resectable PCCA, the PTBD group demonstrated lower rates of crossover (RD = 0.29; 95% CI 0.07–0.51; p = 0.009 I2 = 90%), post-drainage complications (RD = 0.20; 95% CI 0.06–0.33; p < 0.0001; I2 = 78%), and post-drainage pancreatitis (RD = 0.10; 95% CI 0.05–0.16; p < 0.0001; I2 = 64%). The EBD group presented reduced length of hospital stay (RD = -2.89; 95% CI -3.35 - -2,43; p < 0.00001; I2 = 42%). Considering palliative PCCA, the PTBD group demonstrated a higher clinical success (RD = -0.19; 95% CI -0.27 - -0.11; p < 0.00001; I2 = 0%) and less post-drainage cholangitis (RD = 0.08; 95% CI 0.01-0.15; p = 0.02; I2 = 48%) when compared to the EBD group. There was no statistical difference between the groups regarding: technical success, post-drainage bleeding, major post-drainage complications, and seeding metastases. PCCA (PCCA PTBD. . (PTBD) preferred account metanalysis cholangitis, (cholangitis bleeding , complications) metastases MD. MD (MD) 228 1239 1045. 1045 1045) RD 0.29 029 0 29 95 0.07–0.51 007051 07 51 0009 009 0.00 I 90%, 90 90% 90%) postdrainage 0.20 020 20 0.06–0.33 006033 06 33 0.0001 00001 0001 78%, 78 78% 78%) 0.10 010 10 0.05–0.16 005016 05 16 64%. 64 64% 64%) 2.89 289 2 89 -2.89 3.35 335 3 35 -3.3 2,43 243 43 -2,43 0.00001 000001 42%. 42 42% 42%) 0.19 019 19 -0.19 0.27 027 27 -0.2 0.11 011 11 -0.11 0% 0.08 008 08 0.010.15 001015 0.01 0.15 01 15 0.01-0.15 0.02 002 02 48% 48 regarding (PTBD (MD 22 123 104 0.2 9 0.07–0.5 00705 5 000 00 0.0 0.06–0.3 00603 0.000 0000 7 0.1 1 0.05–0.1 00501 6 2.8 28 8 -2.8 3.3 -3. 2,4 24 4 -2,4 0.0000 00000 -0.1 -0. 0.010.1 00101 001 015 0.01-0.1 12 0. 0.07–0. 0070 0.06–0. 0060 0.05–0. 0050 2. -2. 3. -3 2, -2, -0 0.010. 0010 0.01-0. 0.07–0 007 0.06–0 006 0.05–0 005 -2 0.010 0.01-0 0.07– 0.06– 0.05– 0.01- 0.07 0.06 0.05