Objective To investigate the application value of early and delayed laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGD) in 65 years of age or older patients with severe acute cholecystitis. Methods The prospective study was conducted. The clinical data of 80 patients with severe acute cholecystitis who were admitted to Shanxi Dayi Hospital of Shanxi Academy of Medical Sciences from May 2016 to January 2018 were collected. All patients were divided into two groups by random number table, including patients undergoing LC 72 h later after extubation of PTGD in the PTGD + early LC group, and patients undergoing LC 5-14 days later after extubation of PTGD in the PTGD + delayed LC group. Observation indicators: (1) surgical situations; (2) analysis of liver function before and after LC in the two groups; (3) analysis of serum-related inflammatory factors before and after LC in the two groups; (4) follow-up situations. Patients were followed up by outpatient examination or telephone interview to detect the postoperative complications in the postoperative three months up to April 2018. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was done using the paired t test. Count data were represented as absolute number, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results Eighty patients were screened for eligibility, including 41 males and 39 females, aged from 65 to 70 years, with an average age of 67 years. There were 40 patients in the PTGD + early LC group and 40 in the PTGD + delayed LC group, respectively. (1) Surgical situations: the operation time, volume of intra-operative blood loss, and duration of postoperative hospital stay were (52±15)minutes, (29±11)mL, (18.9±1.6)days in the PTGD + early LC group, and (88±13)minutes, (69±11)mL, (27.7±4.8)days in the PTGD + delayed LC group, respectively, showing significant differences in the above indicators between the two groups (t=11.668, 16.219, 11.000, P 0.05), meanwhile, there were significant differences in the levels of AST, ALT, ALP, GGT, TBil after LC between the two groups (t=2.683, 10.067, 19.931, 6.508, 2.380, P 0.05), meanwhile, there were significant differences in the levels of IL-1, IL-6, high-sensitivity CRP, and TNF-α after LC between the two groups (t=24.844, 13.092, 4.833, 15.185, P<0.05). (4) Follow-up situations: 80 patients were followed up for 3 months. Two patients in the PTGD + early LC group had postoperative complications, including 1 of bile duct injury and 1 of incisional infection; 9 patients of PTGD + delayed LC group had postoperative complications, including 3 of bile duct injury, 3 of multiple organ failure, 2 of incisional infection, 1 of death. There was a significant difference in the postoperative complication between the two groups (χ2=5.165, P<0.05). Conclusion Early LC after PTGD can effectively shorten operation time, reduce volume of intraoperative blood loss, shorten duration of postoperative hospital stay, protect liver function, reduce the expression of serum inflammatory factors at 24 hours after surgery, and reduce postoperative complications. Key words: Severe acute cholecystitis; Percutaneous transhepatic gallbladder drainage; Cholecystectomy; Early surgery; Delayed surgery; Laparoscopy