OBJECTIVES: Extracorporeal membrane oxygenation is increasingly used in critically ill patients with refractory cardiopulmonary failure. Nosocomial infection acquired during extracorporeal membrane oxygenation represents one of the most frequent complications but the available evidence on the risk of infection and its association with outcomes has not been comprehensively analyzed. We performed a narrative review examining the epidemiology of nosocomial infection during extracorporeal membrane oxygenation, association with clinical outcomes, and preventive strategies. DATA SOURCES: We searched PubMed, Web of Science, EMBASE, and the Cochrane Library between 1972 and June 2018. STUDY SELECTION: We included any article which detailed nosocomial infection during extracorporeal membrane oxygenation. Articles were excluded if they were not written in English, detailed extracorporeal membrane oxygenation use for infections acquired prior to extracorporeal membrane oxygenation, or used other forms of extracorporeal support such as ventricular assist devices. DATA EXTRACTION: Two reviewers independently assessed eligibility and extracted data. We screened 984 abstracts and included 59 articles in the final review. DATA SYNTHESIS: The reported risk of nosocomial infection among patients receiving extracorporeal membrane oxygenation ranged from 3.5% to 64% per extracorporeal membrane oxygenation run, while the incidence of infection ranged from 10.1 to 116.2/1,000 extracorporeal membrane oxygenation days. Nosocomial infections during extracorporeal membrane oxygenation were consistently associated with longer duration of extracorporeal membrane oxygenation and, in several large multicenter studies, with increased mortality. Risk factors for nosocomial infection included duration of extracorporeal membrane oxygenation, mechanical and hemorrhagic complications on extracorporeal membrane oxygenation, and use of venoarterial and central extracorporeal membrane oxygenation. Biomarkers had low specificity for infection in this population. Few studies examined strategies on how to prevent nosocomial infection on extracorporeal membrane oxygenation. CONCLUSIONS: Nosocomial infections in extracorporeal membrane oxygenation patients are common and associated with worse outcomes. There is substantial variation in the rates of reported infection, and thus, it is possible that some may be preventable. The evidence for current diagnostic, preventive, and therapeutic strategies for infection during extracorporeal membrane oxygenation is limited and requires further investigation.