Objective: The aim of this study was to investigate the association between the use of statins and the occurrence of delirium in a large cohort of patients in the intensive care unit (ICU), considering disease severity and statin properties. Methods: We obtained clinical and demographical information from 3,604 patients admitted to the ICU from January 2013 to April 2020. This included information on daily statin use and delirium state, as assessed by the Confusion Assessment Method for ICU. We used inverse probability of treatment weighting and categorized the patients into four groups based on the Acute Physiology and Chronic Health Evaluation II score (group 1: 0−10 - mild; group 2: 11−20 -mild to moderate; group 3: 21−30 - moderate to severe; group 4: ＞ 30 - severe). We analyzed the association between the use of statin and the occurrence of delirium in each group, while taking into account the properties of statins. Results: Comparisons between statin and non-statin patient groups revealed that only in group 2, patients who were administered statin showed significantly higher occurrence of delirium (p = 0.004, odds ratio [OR] = 1.58) compared to the patients who did not receive statin. Regardless of whether statins were lipophilic (p = 0.036, OR = 1.47) or hydrophilic (p = 0.032, OR = 1.84), the occurrence of delirium was higher only in patients from group 2. Conclusion The use of statins may be associated with the increases in the risk of delirium occurrence in patients with mild to moderate disease severity, irrespective of statin properties.