BACKGROUND: Statins, acknowledged for their ability to reduce cardiovascular risk, demonstrate a variety of pleiotropic effects, including anti-inflammatory, antithrombotic, endothelial stabilizing activity and prevention of acute kidney injury (AKI) post cardiac surgery. Patients in the intensive care unit (ICU) face heightened risks of cardiovascular disease, infections, and thrombotic complications, but the effect of statin therapy on ICU mortality remains controversial. The Medical Information Mart for Intensive Care IV (MIMIC-IV) database is a publicly available intensive care medicine information database that includes data on critically ill patients admitted to the ICU at Beth Israel Deaconess Medical Center from 2008 to 2019, with a large sample size. In this retrospective cohort study, the MIMIC-IV database was used to clarify the association between statin therapy and all-cause mortality in critically ill patients. An additional aim was to compare the effect of different statin types on mortality. METHODS: Patients aged 18 years or older, with first-time admissions and complete data, were categorized based on their use of statins during their ICU stay. The primary outcome was 28-day mortality, analyzed through multivariable Cox regression and expressed as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). The relationship between statin therapy and 28-day mortality in ICU patients was estimated using propensity score matching (PSM) and multivariable analysis to adjust for covariates. RESULTS: Among the 50,624 enrolled patients, 30.9% were treated with statins. Compared to patients not receiving statin therapy, those on statins were older, had a higher proportion of males (62.0% CONCLUSIONS: Statin use may correlate with a decreased risk of 28-day mortality in patients in the ICU, with simvastatin showing a more pronounced effect. The robustness of these findings remain unaffected in the subgroup analyses, sensitivity analyses, and PSM, indicating potential clinical significance. The high mortality rate among ICU patients means that any method capable of reducing mortality could have significant implications for ICU treatment.