One of the main problems concerning the design of clinical trials in critically ill patients with acute cholecystitis (AC) is the lack of validated, well-established scoring systems to stratify the severity of patient disease states. The aim of this study was to evaluate the performance of the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system in patients over 65 years with AC. All patients over 65 years of age admitted to our hospital for treatment of AC in the intensive care unit between January 2013 and January 2019 were retrospectively analyzed. A total of 443 consecutive patients with AC were enrolled in this study. As for the patients over 65 years, the survivors had lower APACHE IV scores and lower risk of death than nonsurvivors (P<0.01). The discrimination of the APACHE IV score prediction was good, with an area under the curve of 0.850 (95% confidence interval, 0.780-0.932). The APACHE IV models were well-calibrated with the Hosmer-Lemeshow goodness-of-fit test (P=0.635). Similar results were obtained for patients over 85 years of age. The APACHE IV model was good at predicting hospital mortality in elderly patients with AC, which would be helpful to make clinical and therapeutic decisions in the future.