Background and Aims Acute cholecystitis (AC) is a frequently encountered disease in the general surgical practice. Laparoscopic cholecystectomy (LC) is currently recognized as the "gold-standard" treatment for AC. The severity of AC is recommended to be classified as grade I (mild), Ⅱ (moderate) and Ⅲ (severe) by the Tokyo guidelines 2018 (TG18), and the choice of surgical procedure varies according to the grade of disease. In clinical practice, the consensus has been achieved on the treatment of grade Ⅰ and Ⅲ AC. However, the treatment strategy for grade Ⅱ AC is still controversial, which depends more on the surgeon's experience and the admitting medical provider. The intraoperative conditions are complicated in patients with grade Ⅱ AC, for which inappropriate LC surgery may cause higher incidence of complications, such as bile leakage, abdominal abscess, and even bile duct injury. Percutaneous transhepatic gallbladder drainage (PTGBD) can effectively relieve the inflammation of the gallbladder, gallbladder wall edema and adhesions around the gallbladder, and also provide a "time window" for elective surgery. Therefore, this study was performed to evaluate the application value of sequential LC after PTGBD in the treatment of grade Ⅱ AC.Methods The clinical data of 205 patients classified as grade Ⅱ AC according to TG18 classification in Yixing Hospital Affiliated to Jiangsu University from October 2017 to October 2022 were analyzed retrospectively. Of the patients, 42 cases underwent PTGBD followed by elective LC (PTGBD+LC group) and 163 cases underwent urgent LC (LC group). The two groups of patients were matched using propensity score matching (PSM) at a 1∶1 ratio. After match, the differences in clinical indexes such as ICU admission rate, operative time, intraoperative blood loss, intraoperative drainage rate, open conversion rate, bile duct injury rate, length of hospital stay, total hospitalization cost and surgical complications were compared between the two groups of patients.Results No puncture-related complications occurred in the 42 patients who received PTGBD. Only one patient had catheter slippage and underwent catheter re-insertion. All the 42 patients received a questionnaire survey on the quality of life during indwelling catheterization, and the results showed that 39 patients (92.8%) tolerated the treatment. There were 38 patients in each group after match, with balanced and comparable baseline data. There was no perioperative death in both groups. In PTGBD+LC group, the operative time was shorter (64.4 min vs. 84.4 min), intraoperative blood loss was less (21.9 mL vs. 47.6 mL), length of hospital stay after LC was shorter (3.4 d vs. 5.3 d), and overall incidence of postoperative complications was lower (5.3% vs. 23.7%), but the total hospitalization cost was higher (29 239 yuan vs. 22 150 yuan) than those in LC group, and all differences had statistical significance (all P<0.05). There were no significant differences in rates of open conversion (0 vs. 13.2%), bile duct injury (0 vs. 5.3%), intraoperative drainage (92.1% vs. 100%) and postoperative ICU admission (0 vs. 5.3%) between the two groups (P>0.05).Conclusion Sequential LC after PTGBD in the treatment of TG18 grade Ⅱ AC increases the total medical cost, but significantly reduce the difficulty of surgery and the incidence of surgical-related complications. So, it is still suitable for individualized application in clinical practice.