ObjectiveWe aimed to investigate the characteristics of nosocomial infections (NIs) and the impact of prophylactic antibiotic administration on NI outcomes in patients who underwent extracorporeal cardiopulmonary resuscitation (ECPR). MethodsThis retrospective study analyzed the rate, type, pathogens, outcomes, and risk factors of NIs that developed in adult patients who underwent ECPR at our institution between January 2002 and January 2022. ResultsAmong 105 patients (median age, 58.59 [interquartile range, 46.53-67.32] years), 57 (54.29%) patients developed NIs during their extracorporeal membrane oxygenation courses. The incidence rates per 1000 extracorporeal membrane oxygenation days were 135.91 for overall infections and 40.06 for multidrug-resistant (MDR) infections. Ventilator-associated pneumonia was the most common type of NI (73.68%), followed by bloodstream infections (17.89%). Prophylactic antibiotics with Pseudomonas aeruginosa coverage were protective factors against NI (hazard ratio [HR], 0.518; 95% confidence interval [CI], 0.281-0.953; P = .034). High dynamic driving pressure of the ventilator (cmH2O) was a prognostic factor for hospital mortality (HR, 1.096; 95% CI, 1.008-1.192; P = .032). An Acute Physiology and Chronic Health Evaluation II score of ≥24 (HR, 6.443; 95% CI, 1.380-30.088; P = .018) was a risk factor for developing MDR infections. ConclusionsIn patients who undergo ECPR, prophylactic antibiotic treatment with P aeruginosa coverage is associated with a lower incidence of NIs, whereas an Aeruginosa Acute Physiology and Chronic Health Evaluation II score of ≥24 is a risk factor for MDR infections. In the modern era of antibiotic therapy, the development of NIs does not increase hospital mortality among patients undergoing ECPR.