Objective: Although described >70 y ago, the refeeding syndrome (RFS) remains understudied with lack of standardized definition and treatment recommendations. The aim of this systematic review was to gather evidence regarding standardized definition, incidence rate and time course of occurrence, association with adverse clinical outcomes, risk factors, and therapeutic strategies to prevent or treat this condition. Methods: We searched MEDLINE and EMBASE for interventional and observational clinical trials focusing on RFS, excluding case reports and reviews. We extracted data based on a predefined case report form and assessed bias. Results: Of 2207 potential abstracts, 45 records with a total of 6608 patients were included (3 interventional trials, 16 studies focusing on anorexic patients). Definitions for RFS were highly heterogenous with most studies relying on blood electrolyte disturbances only and others also including clinical symptoms. Incidence rates varied between 0% and 80%, depending on the definition and patient population studied. Occurrence was mostly within the first 72 h of start of nutritional therapy. Most of the risk factors were in accordance with National Institute for Health and Care Excellence guidelines, with older age and enteral feeding being additional factors. There was no strong evidence regarding association of RFS and adverse outcomes, as well as regarding preventive measures and treatment algorithms. Conclusion: This systematic review focusing on RFS found consensus regarding risk factors and timing of occurrence, but wide variations regarding definition, reported incidence rates, preventive measures and treatment recommendations. Further research to fill this gap is urgently needed. (C) 2016 Elsevier Inc. All rights reserved.