This study aimed to evaluate the timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD). Patients with acute moderate to severe cholecystitis treated by LC after PTGBD in the Department of Hepatobiliary and Pancreatic Surgery, Nankai Hospital (N-362) between January 2017 and August 2019were retrospectively enrolled into this study. According to the interval times from PTGBD to LC, the patients were divided into six groups, including group A (105 cases, within 1 week), group B (62 cases, 1-2 weeks), group C (34 cases, 3-4 weeks), group D (54 cases, 5-8 weeks), group E (24 cases, 9-12 weeks), and group F (83 cases, over 12 weeks). The gender, age, hospital stay, duration of operation, rate of conversion to laparotomy, incidence of complications, and hospitalization expenses of the six groups were evaluated and compared. Of the 362 cases of LC, 346 patients were operated successfully (95.6%), 10 were converted to laparotomy (2.8%), 16 had various complications (4.4%), and 2 died (0.6%). There were no significant differences between groups in the gender ratio, complication rate, and rate of conversion to laparotomy. The hospital stay and hospitalization expenses in group A were the least and significantly lower than those in other groups (P<0.01), and the duration of operation in group D was the longest and significantly higher than that in groups A, B, E, and F (P<0.05). For non-elderly patients diagnosed with acute moderate to severe cholecystitis with an anesthesia risk score [American Society of Anesthesiologists (ASA)] ≤2, LC is recommended to be performed within 1 week after PTGBD surgery. If delayed LC is performed within 2 to 8 weeks after PTGBD, the operation time will be longer due to inflammatory edema and fibrous adhesion of the gallbladder triangle. If PTGBD is performed for more than 2 months and the clinical circumstances are good, delayed LC can be considered to reduce the inconvenience of patients with a long-term catheter as much as possible.