Background: The critically ill and surgical patients are at significant risk of delirium, which is associated with a high morbidity and mortality. The association between statin use and the incidence of delirium is still controversial. In this article, we will perform a systematic review and meta-analysis of published studies to evaluate the effectiveness of statins for the prophylaxis of delirium among critically ill and surgical patients. Methods: We will conduct a systematic literature search in EMBASE, PubMed, and the Cochrane Library from inception date to October 2018 for randomized controlled trials (RCTs) and observational studies (either cohort or case-control studies) investigating the association between use of statins and delirium risk. The Cochrane Collaboration's tool for evaluating the risk of bias and Newcastle-Ottawa scale (NOS) will be used to assess the methodological quality of RCTs and observational studies, separately. The primary outcome will be the risk of incident delirium associated with statin use. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) will be calculated by a random-effects or fixed-effects model according to heterogeneity among included studies. Subgroup analyses. meta-regression method, and assessment of publication bias will be also performed. Statistical analyses will be conducted with RevMan (version 5.3.5) and Stata (version 14.0) software. In addition, the grading of recommendations assessment, development and evaluation (GRADE) approach will be applied to evaluate the quality of evidence. Results: The study will provide a high-quality synthesis and evaluate the effectiveness of statins for delirium prevention among critically ill and surgical patients. Conclusions: The systematic review and meta-analysis will provide convincing evidence concerning the effect of statins against delirium in critically ill and surgical patients.