Objective To explore the effects of percutaneous transhepatic gallbladder drainage （PTGBD） and percutaneous transhepatic gallbladder aspiration （PTGBA） on moderate to severe acute cholecystitis. Methods A total of 96 patients with moderate to severe acute cholecystitis admitted from May 2018 to June 2020 were selected and divided into a control group and a study group according to random number table method, with 48 cases in each group. The control group was treated with PTGBD, and the study group was treated with PTGBA. The clinical efficacy, perioperative indications, inflammation indicators, and complications of the two groups were observed. Results The clinical efficacy of the study group was better than that of the control group （P<0.05）, and the hospital stay was shorter （P<0.05）. There was no significant difference in operation time between the two groups （P>0.05）. The levels of white blood cells, C-reactive protein （CRP）, and serum amyloid （SAA） in the study group were lower than those in the control group 72 h after surgery （P<0.05）. The complication rate of the study group was 6.25%, lower than 20.84% of the control group （P<0.05）. Conclusion Compared with PTGBD, PTGBA can quickly reduce the inflammation level and postoperative complication incidences in patients with moderate to severe acute cholecystitis, improve treatment effect, and promote their rapid recovery.