Abstract:Objective To compare the differences in drainage efficacy，pain，inflammatory response，and complications between peroral cholangioscopy（POCS）-assisted endoscopic transpapillary gallbladder drainage（ETGBD）and percutaneous transhepatic gallbladder drainage （PTGBD）in patients with moderate to severe acute cholecystitis.Methods A retrospective analysis was performed on the clinical data of 60 patients with moderate to severe acute cholecystitis admitted to the Cholelithiasis Diagnosis and Treatment Center of Wuhan Puren Hospital from January 2024 to June 2025. According to surgical method，the patients were divided into group A（undergoing POCS - assisted ETGBD，n=30）and group B（undergoing PTGBD，n=30）. Drainage success rate was evaluated at 1 - week after operation. Abdominal pain was assessed using the Visual Analogue Scale（VAS）at 1-day，and 3-day and 1-week after operation. White blood cell count（WBC），and C-reactive protein（CRP）levels were also measured at 3-days and（2024）1 - week after operation. Complications including cholecystitis recurrence，bleeding，and bile leakage were recorded during hospitalization. Operation time，length of hospitalization，and hospitalization cost were compared between two groups. Perioperative quality of life was assessed using the 36-Item Short Form Health Survey（SF-36）scale. Results There was no significant difference in drainage success rate between group A and group B（93.3% vs 90.0%，χ²=0，P=1.000）.The values of VAS scores，WBC and CRP showed statistically significant differences in inter -time effect，inter-group effect，and interaction effect（P<0.05）. Postoperatively，VAS scores，WBC，and CRP decreased in both groups（P<0.05），and group A had lower WBC at 3-day after operation，as well as lower VAS and CRP at all postoperative time points compared to group B（P<0.05）. Group A had longer operation time，higher hospitalization cost，and shorter length of hospitalization compared to group B（P<0.05）. At 1-week after operation，group A had significantly higher physical function，social function，and emotional role scores in the SF-36 scale compared to group B（P<0.05）. The incidence of complications in group A was slightly lower than that in group B，but the difference was not statistically significant（10.0% vs 26.7%，χ²=2.783，P=0.095）. Conclusion POCS-assisted ETGBD and PTGBD have similar success rates of drainage in the treatment of moderate to severe acute cholecystitis. However，POCS - assisted ETGBD shows advantages in reducing WBC and CRP levels，providing a safe and effective alternative for patients with moderate to severe acute cholecystitis.