Purpose: In the Tokyo Guidelines 2018 (TG18), emergency laparoscopic cholecystectomy is recognized as a crucial early treatment option for acute cholecystitis. However, early laparoscopic intervention in patients with moderate-to-severe acute cholecystitis or those with severe comorbidities may increase the risk of complications. Therefore, in the present study, we investigated the association between early laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) in moderate-to-severe acute cholecystitis patients. Methods: We retrospectively analyzed 835 TG18 grade II or III acute cholecystitis patients who underwent laparoscopic cholecystectomy at 4 tertiary medical centers in the Republic of Korea. Patients were classified into 2 groups according to whether PTGBD was performed before surgery, and their short-term postoperative outcomes were analyzed retrospectively. Results: The patients were divided into 2 groups, and 1:1 propensity score matching was conducted to establish the PTGBD group (n = 201) and the early laparoscopic cholecystectomy group (n = 201). The PTGBD group experienced significantly higher rates of preoperative systemic inflammatory response syndrome (24.9% vs. 6.5%, P < 0.001), pneumonia (7.5% vs.3.0%, P = 0.045), and cardiac disease (67.2% vs. 57.7%, P = 0.041) than the early operation group. However, there was no difference in biliary complication (hazard ratio, 1.103; 95% confidence interval, 0.519–2.343; P = 0.799) between the PTGBD group and early laparoscopic cholecystectomy group. Conclusion In most cases of moderate-to-severe cholecystitis, early laparoscopic cholecystectomy was relatively feasible.However, PTGBD should be considered if patients have the risk factor of underlying disease when experiencing general anesthesia.