OBJECTIVE:Diphoterine is a hypertonic, amphoteric, polyvalent and chelating decontamination solution used in the treatment of cutaneous and ocular chemical burns. Due to infrequent use by emergency physicians along with the small number of available studies, its debate in the literature as to its efficacy and safety remains inconclusive. METHODS:A structured literature search was performed in MEDLINE, EMBASE BIOLOGICAL ABSTRACTS and TOXNET to June 2016 for original English-language studies reporting on the safety and effectiveness of Diphoterine. Methodological and reporting quality of pre-clinical animal studies was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Clinical studies were assessed using Chambers' criteria. RESULTS:13 studies (seven in the pre-clinical, five in the clinical setting and one mixed) met the study inclusion criteria. Pre-clinical studies showed a faster resolution of pH and reduced tissue necrosis with Diphoterine. Clinical studies showed reduced tissue necrosis/severity of symptoms, faster pH resolution and a reduction in pain when using Diphoterine. No adverse events were attributable to Diphoterine. Reporting and methodology of the studies was poor or showed a high risk of bias. CONCLUSIONS:Diphoterine appears to be safe to use and is probably superior to other rinsing solutions. However, immediate decontamination is imperative and if Diphoterine is not available a different rinsing solution should be used. The methodology of the published literature for Diphoterine is generally poor and future publications should use the frameworks given as templates.