BackgroundPreoperative anemia is a common and potentially serious hematological problem in elective surgery and increases the risk for perioperative red blood cell (RBC) transfusion. Transfusion is associated with postoperative morbidity and mortality. Preoperative intravenous (IV) iron therapy has been proposed as an intervention to reduce perioperative transfusion; however, studies are generally small, limited, and inconclusive.Methods/DesignWe propose performing a systematic review and meta-analysis. We will search MEDLINE, EMBASE, EBM Reviews, Cochrane-controlled trial registry, Scopus, registries of health technology assessment and clinical trials, Web of Science, ProQuest Dissertations and Theses, and conference proceedings in transfusion, hematology, and surgery. We will contact our study drug manufacturer for unpublished trials. Titles and abstracts will be identified and assessed by two reviewers for potential relevance. Eligible studies are: randomized or quasi-randomized clinical trials comparing preoperative administration of IV iron with placebo or standard of care to reduce perioperative blood transfusion in anemic patients undergoing major surgery. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Data will be presented in evidence tables and in meta-analytic forest plots.Primary efficacy outcomes are change in hemoglobin concentration and proportion of patients requiring RBC transfusion. Secondary outcomes include number of units of blood or blood products transfused perioperatively, transfusion-related acute lung injury, neurologic complications, adverse events, postoperative infections, cardiopulmonary complications, intensive care unit (ICU) admission/readmission, length of hospital stay, acute kidney injury, and mortality.Dichotomous outcomes will be reported as pooled relative risks and 95% confidence intervals. Continuous outcomes will be reported using calculated weighted mean differences. Meta-regression will be performed to evaluate the impact of potential confounding variables on study effect estimates.DiscussionReducing unnecessary RBC transfusions in perioperative medicine is a clinical priority. This involves the identification of patients at risk of receiving transfusions along with blood conservation strategies. Of potential pharmacological blood conservation strategies, IV iron is a compelling intervention to treat preoperative anemia; however, existing data are uncertain. We propose performing a systematic review and meta-analysis evaluating the efficacy and safety of IV iron administration to anemic patients undergoing major surgery to reduce transfusion and perioperative morbidity and mortality.Systematic review registrationPROSPERO CRD42015016771Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0016-4) contains supplementary material, which is available to authorized users.