The aim of this study is to compare the efficacy and complication rates of percutaneous gallbladder aspiration (PA) and percutaneous cholecystostomy (PC) in the management of AC and present the experiences of a single third-line center. The results of 159 patients with AC who admitted to our hospital between 2015 and 2020, that underwent PA and PC procedures, because they did not respond to conservative treatment and LC could not be performed, were retrospectively analyzed. Clinical and laboratory data before and 3 days after PC and PA procedure, technical success, complications, response to treatment, duration of hospital stay, and reverse transcriptase-polymerase chain reaction (RT-PCR) test results were recorded. Out of 159 patients, 22 (8 men 14 women) underwent PA procedure and 137 (57 men 80 women) underwent PC. No significant difference was detected between the PA and PC groups in terms of clinical recovery (P: 0.532) and duration of hospital stay (P: 0.138) in 72 h. The technical success of both procedures was 100%. While 20 out of 22 patients with PA were having a noticable recovery, only one was treated with twice PA procedures and a complete recovery was observed (4.5%). Complication rates were low in both groups and were statistically insignificant (P: 1.00). In this pandemic period, PA and PC procedures are effective, reliable, and successful treatment method that can be applied at the bedside for critical patients with AC who are not compatible with surgery, which are safe for health workers and low-risk minimal invasive procedures for patients. In uncomplicated AC patients, PA should be performed, and if there is no response to treatment, PC should be reserved as a salvage procedure. The PC procedure should be performed in patients with AC who have developed complications and are not suitable for surgery.