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OBJECTIVES:. The objective of this review was to depict the physiological and clinical rationale for the use of vasopressin in hemodynamic support of organ donors. After summarizing the physiological, pharmacological concepts and preclinical findings, regarding vasopressin’s pathophysiological impacts, we will present the available clinical data. DATA SOURCES:. Detailed search strategies in PubMed, OVID Medline, and EMBASE were undertaken using Medical Subject Headings and Key Words. STUDY SELECTION:. Physiological articles regarding brain death, and preclinical animal and human studies about the use of vasopressin or analogs, as an intervention in organ support for donation, were considered. DATA EXTRACTION:. Two authors independently screened titles, abstracts, and full text of articles to determine eligibility. Data encompassing models, population, methodology, outcomes, and relevant concepts were extracted. DATA SYNTHESIS:. Following brain death, profound reduction in sympathetic outflow is associated with reduced cardiac output, vascular tone, and hemodynamic instability in donors. In addition to reducing catecholamine needs and reversing diabetes insipidus, vasopressin has been shown to limit pulmonary injury and decrease systemic inflammatory response in animals. Several observational studies show the benefit of vasopressin on hemodynamic parameters and catecholamine sparing in donors. Small trials suggest that vasopressin increase organ procurement and have some survival benefit for recipients. However, the risk of bias is overall concerning, and therefore the quality of the evidence is deemed low. CONCLUSIONS:. Despite potential impact on graft outcome and a protective effect through catecholamine support sparing, the benefit of vasopressin use in organ donors is based on low evidence. Well-designed observational and randomized controlled trials are warranted.