Purpose <p>Secondary injury after trauma is responsible for significant morbidity and mortality. Inflammation appears to play a central role. Some evidence proposes that statins (HMG-CoA reductase inhibitors) may modulate this inflammation via their pleiotropic properties (non-cholesterol lowering effects). These include suppression of complement activation, vasodilation and inhibition of platelet function and aggregation. The purpose of this systematic review and meta-analysis was to investigate whether pre-morbid statin use is associated with differences in outcomes after trauma.</p> Methods <p>MEDLINE, EMBASE, Central, Google Scholar, clinicaltrials.gov, clinicaltrialsregister.eu and the German clinical trials register were searched for articles published between 01.09.1987 and 31.12.2023 examining pre-morbid statin use on outcomes after trauma.</p> Results <p>After removal of duplicates, 623 records for abstract review were identified, of which nine were included in the systematic review and eight the meta-analysis. All studies were retrospective and most did not confirm in-hospital administration of pre-morbid statins. All had a high risk of bias. Grading of Recommendations Assessment indicated a very low certainty of results. When considering pre-morbid statin use in all types of trauma, the overall mortality risk ratio was 0.66 (95% CI 0.37–1.17) with high heterogeneity (I2 = 99%). The use of statins before traumatic brain injury (TBI) indicated a mortality risk ratio of 0.60 (95% CI 0.28–1.27, I2 = 96%). Analysis non-TBI studies yielded a risk ratio of 0.84 [95% CI 0.56–1.27].</p> Conclusion <p>In a limited meta-analysis, data failed to demonstrate an association between pre-morbid statin use following serious injury. As this may be due to a heterogeneity in data, variable study population, and a number of confounding factors, further dedicated study is warranted to clarify whether observed associations reflect pharmacologic effects.</p>