Introduction: The optimal stent type for biliary drainage in cholangiocarcinoma (CCA) is not established. Methods: This is a retrospective study of patients with CCA from 1997-2023, excluding Bismuth class 1, who underwent biliary drainage at a cancer center. A per-patient analysis of percutaneous biliary drainage (PBD) rates, median number of ERCPs, overall survival (OS), and a per-procedure analysis of clinical success (CS), stent specific complications (SSCs), and mean time to reintervention by stent type and laterality (u vs b) is presented (Figure 1). Results: Overall, 333 patients underwent 1,127 ERCPs (85% with plastic stents (PS)); PBD was done in 23% of PS patients; 35% had PS removed pre-PBD. ERCPs with SEMS and uSEMS use had higher CS (89%/91%) vs PS/uPS (85% both) and PS within SEMS (PS-SEMS)/uPS-SEMS (71%/74%; P=0.054); PS-SEMS were associated with poorer CS vs PS (OR 0.35;0.15-0.80;P=0.013). More SSCs were noted in SEMS (uSEMS 57%/bSEMS 41%) and PS-SEMS arms (uPS-SEMS 74%/bPS-SEMS 60%;P< 0.001); both were associated with higher SSCs vs PS (OR SEMS 4.85;3.23-7.27; PS-SEMS 9.99;5.33-18.71;P< 0.001). Straight PS were associated with more SSCs vs double-pigtail stents (DPT;OR 6.74;3.95-11.45;P< 0.001). Liver atrophy, pus on ERCP, higher Bismuth class, less CS, PS use, and PS-SEMS use were associated with shorter mean time to repeat ERCP. Balloon dilation (BD) was done in 48% of ERCPs with Bismuth 4 disease. Bilateral stenting was done in 53% of ERCPs with BD. PS were placed in 90% after BD; 41% were DPT; more 7 Fr stents were used (109 vs 88 with no BD;P< 0.001). CS was 79% with BD versus 87% without BD (P< 0.001) (Table 1). Radiotherapy, total ERCPs/ PBDs & internalization of external PBDs were associated with improved OS; 52% of patients in the bSEMS arm had death from cholangitis (DFC) vs uSEMS (32%; P=0.005), with no difference in uPS vs bPS. There was no significant difference in DFC on competing risk analysis stratified by stent type or PBD status. Conclusion: The higher CS with SEMS use comes at the cost of higher SSCs, and potentially higher DFC (with bSEMS). PS removal to facilitate PBD is an advantage over SEMS. DPTs have less SSCs than straight PS. The mean time to repeat ERCP was shorter with PS use, but without difference in number of ERCPs per patient. BD should be utilized to aid in stenting tight strictures. Pus on ERCP and liver atrophy may have predictive potential for time to reintervention.Figure 1.: Schematic of Per-Patient and Per-Procedure Analysis Structure. Table 1. - Characteristics and Outcomes of Biliary Drainage in Peri-Hilar Cholangiocarcinoma – Per-Procedure Analysis Variables Unilateral Stents Bilateral Stents Plastic Stents Metal Stents Plastic in Metal Stents P-value Plastic Stents Metal Stents Plastic in Metal Stents P-value Indication for ERCP, n (%) Cholangitis 73 (14.3) 16 (19) 10 (28.6) 0.022 60 (16) 2 (6.9) 2 (13.3) < 0.001 Stent Exchange 222 (43.4) 24 (28.6) 11 (31.4) 209 (55.7) 8 (27.6) 5 (33.3) Hyperbilirubinemia without Cholangitis 216 (42.3) 44 (52.4) 14 (40) 106 (28.3) 19 (65.5) 8 (53.3) Pus on ERCP, n(%) 63 (12.35) 14 (16.67) 12 (35.29) 0.001 66 (17.55) 6 (20.69) 3 (20) 0.892 Liver Atrophy, n(%) 221 (44.8) 28 (35.4) 15 (44.12) 0.295 117 (31.7) 11 (39.3) 3 (21.4) 0.492 Balloon Dilation, n(%) 350 (68.6) 72 (85.7) 24 (70.6) 0.006 185 (49.2) 10 (34.5) 8 (53.3) 0.288 Balloon Dilation Pattern, n(%) Unilateral Balloon Dilation 135 (88.2) 9 (75) 9 (100) 0.208 70 (38.25) 3 (30) 5 (62.5) 0.326 Bilateral Balloon Dilation 3 (25) 18 (11.7) 0 (0) 113 (61.75) 7 (70) 3 (37.5) Technical Success, n(%) 510 (99.8) 84 (100) 35 (100) NS 376 (100) 29 (100) 15 (100) NS Clinical Success, n(%) 424 (84.5) 72 (91.1%) 25 (73.5) 0.054 313 (84.6) 25 (86.2) 10 (66.6) 0.168 Adverse Events, n(%) 112 (21.9) 48 (57.1) 26 (74.3) < 0.001 56 (14.9) 12 (41.3) 9 (60) < 0.001 Change in Bilirubin After ERCP, mean (SD) 0.04 (1.10) 0.07 (1.51) 0.07 (0.70) NS 0.01 (1.13) 0.35 (0.42) 0.22 (0.95) NS Time to repeat ERCP (days), mean (SD) 72.6 (85.3) 250.8 (46) 57.4 (29.2) NS 75.4 (43.0) 133.8 (136.1) 48.5 (29.4) NS Univariate and Multivariate Regression – Mean Time to Repeat ERCP Univariate Analysis, Coef (P-value) Univariate Analysis, Coef (P-value) Liver Atrophy Yes -23.01 (0.005) -15.76 (0.002) Pus on ERCP Yes -18.4 (0.09) -15.71 (0.092) Bismuth Classification 2 Ref 3a -43.6 (< 0.001) -34.1 (< 0.001) 3b -34.1 (0.001) -30.81 (0.001) 4 -42.8 (< 0.001) -33.93 (< 0.001) Balloon Dilation Yes -14.33 (0.074) Clinical Success Yes 52.2 (< 0.001) 43.2 (< 0.001) Adverse Events Yes 11.72 (0.193) Stent Categories Plastic Stents -143.9 (< 0.001) -145.3 (< 0.001) Plastic Stents within Metal Stents -163.5 (< 0.001) -147.7 (< 0.001) Univariate and Multivariate Regression – Stent Specific Complications Univariate Analysis, Coef (P-value) Multivariate Analysis , Coef (P-value) Liver Atrophy Yes 1.613 (1.216, 2.140; 0.001) Pus on ERCP Yes 1.6683 (1.1712, 2.3764; 0.005) 1.9466 (1.0940, 3.4634; 0.023) Bismuth Classification 2 Ref 3a 0.6527 (0.4247, 1.0031; 0.052) 3b 0.6720 (0.4612, 0.9792; 0.039) 4 0.9870 (0.6911, 1.4094; 0.942) Balloon Dilation Yes 0.6390 (0.4743, 0.8609; 0.003) Time to Repeat ERCP 1.001 (0.9995, 1.002; 0.201) 1.0025 (1.0000, 1.0050; 0.049) Clinical Success Yes 0.961 (0.662, 1.396; 0.834) Stent Categories Metal Stents Ref Plastic Stents 0.2064 (0.138, 0.310; < 0.001) Plastic Stents within Metal Stents 2.061 (1.015, 4.187; 0.046) Univariate and Multivariate Regression – Clinical Success of ERCP Univariate Analysis, Coef (P-value) Multivariate Analysis , Coef (P-value) Liver Atrophy Yes 1.0074 (0.7123 - 1.428; 0.967) Pus on ERCP Yes 0.8023 (0.5188 - 1.2407; 0.322) Bismuth Classification 2 Ref 3a 0.635 (0.372-1.086; 0.097) 3b 0.613 (0.378 - 0.993; 0.047) 4 0.490 (0.306 - 0.783; 0.003) Balloon Dilation Yes 0.526 (0.377 - 0.734; 0.000) 0.5448 (0.3312, 0.8960; 0.017) Time to Repeat ERCP 1.034 (1.026 - 1.043; < 0.001) 1.032 (1.023, 1.041; < 0.001) Adverse Events Yes 0.961 (0.662 - 1.396; 0.834) Stent Categories Metal Stents Ref Plastic Stents 0.619 (0.323 - 1.186; 0.148) 2.2625 (0.7199, 7.1105; 0.162) Plastic Stents in Metal Stents 0.284 (0.118 - 0.68; 0.005) 0.7836 (0.1997, 3.0753; 0.727) Plastic Stents Ref Plastic Stents in Metal Stents 0.458 (0.240, 0.874; 0.018) 0.346 (0.150, 0.798; 0.013)