Abstract Objectives This study aimed to investigate the efficacy of ultrasound-guided Percutaneous Transhepatic Biliary Drainage (PTCD) for the treatment of Acute Obstructive Suppurative Cholangitis (AOSC) combined with septic shock due to choledocholithiasis, and its effect on inflammatory factors. Methods Clinical data of 86 patients with AOSC and septic shock admitted to our hospital between January 2019 and May 2021 were retrospectively analyzed and grouped according to different treatment methods. Among them, 43 patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Nasobiliary Drainage (ENBD) were included in the Control Group (CNG), and 43 patients who underwent ultrasound-guided PTCD were included in the Study Group (SG). Results The total effective rate in the SG (88.37%) was higher than that in the CNG (69.77%) (p <0.05); after surgery, the serum inflammatory factors PCT, IL-6, TNF-α, CRP levels, liver function indicators such as TBIL, DBIL, AST, ALT levels, and stress response indicators including NPY, PGE2, 5-HT levels were reduced, and were lower in the SG than in the CNG (p <0.05); postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the CNG were significantly lower than those before surgery (p <0.05); Postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the SG were significantly higher than those in the CNG (p <0.05); and the complication rate in the SG (6.98%) was lower than that in the CNG (25.58%) (p <0.05). Conclusions Ultrasound-guided PTCD for AOSC combined with septic shock can facilitate the recovery of liver and immune functions with a low complication rate. ultrasoundguided ultrasound guided (PTCD (AOSC choledocholithiasis 8 201 202 methods them 4 ERCP (ERCP ENBD (ENBD CNG, , (CNG) SG. . (SG) 88.37% 8837 88 37 (88.37% 69.77% 6977 69 77 (69.77% p <0.05 005 0 05 <0.05) PCT IL6, IL6 IL 6, 6 IL-6 TNFα, TNFα TNF α, α TNF-α TBIL DBIL AST NPY PGE2 PGE 5HT HT 5 reduced postoperatively CD3 CD CD3+ CD4 CD4+ CD4CD8 CDCD CD8 CD4+/CD8 Postoperatively 6.98% 698 98 (6.98% 25.58% 2558 25 58 (25.58% <0.05. Ultrasoundguided Ultrasound 20 (CNG (SG 88.37 883 3 (88.37 69.77 697 7 (69.77 <0.0 00 IL- CD4CD CD4+/CD 6.98 9 (6.98 25.58 255 2 (25.58 88.3 (88.3 69.7 (69.7 <0. 6.9 (6.9 25.5 (25.5 88. (88. 69. (69. <0 6. (6. 25. (25. (88 (69 < (6 (25 (8 ( (2