This systematic review was conducted to assess the evidence for using heparin to treat burn injury. The following databases were searched for relevant studies: MEDLINE, EMBASE, CINAHL, The Cochrane Central Database of Controlled Trials, Web of Science, and BIOSIS. Additional searches involved the reference lists of included studies, the "grey " literature (eg, government reports), and consultations with experts to obtain unpublished manuscripts. Included studies were summarized descriptively and in tabular form, and assessed for methodological quality. A metaanalysis was conducted to obtain a summary estimate for the association between heparin use and postburn mortality. Nine studies were abstracted and included in the review. Five studies contained adult and pediatric patients, one contained adults only, and three contained pediatric patients only. Burn etiologies included flame, scald, thermal, or smoke inhalation. Heparin administration was done topically, subcutaneously, intravenously, or via aerosol. Heparin was reported to have a beneficial impact on mortality, graft and wound healing, and pain control. For mortality, the overall estimate (relative risk) of heparin's effect was 0.32 (95% confidence interval = 0.18-0.57). Heparin's reported benefits may be severely biased because the abstracted studies were beset by poor methodological quality (eg, inadequate definitions of treatment and outcome, no control of confounding). Given poor study quality, there is no strong evidence to indicate that heparin can improve clinical outcomes in the treatment of burn injury. Further research is needed to assess the clinical utility of using heparin in the treatment of burn injury.