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To study incidence, type, etiology, risk factors, and impact on outcome of nosocomial infections during extracorporeal membrane oxygenation.Retrospective analysis of prospectively collected data.Italian tertiary referral center medical-surgical ICU.One hundred five consecutive patients who were treated with extracorporeal membrane oxygenation from January 2010 to November 2015.None.Ninety-two patients were included in the analysis (48.5 [37–56] years old, simplified acute physiology score II 37 [32–47]) who underwent peripheral extracorporeal membrane oxygenation (87% veno-venous) for medical indications (78% acute respiratory distress syndrome). Fifty-two patients (55%) were infected (50.4 infections/1,000 person-days of extracorporeal membrane oxygenation). We identified 32 ventilator-associated pneumonia, eight urinary tract infections, five blood stream infections, three catheter-related blood stream infections, two colitis, one extracorporeal membrane oxygenation cannula infection, and one pulmonary-catheter infection. G+ infections (35%) occurred earlier compared with G– (48%) (4 [2–10] vs. 13 [7–23] days from extracorporeal membrane oxygenation initiation; p < 0.001). Multidrug-resistant organisms caused 56% of bacterial infections. Younger age (2–35 years old) was independently associated with higher risk for nosocomial infections. Twenty-nine patients (31.5%) died (13.0 deaths/1,000 person-days of extracorporeal membrane oxygenation). Infected patients had higher risk for death (18 vs. 8 deaths/1,000 person-days of extracorporeal membrane oxygenation; p = 0.037) and longer ICU stay (32.5 [19.5–78] vs. 19 [10.5–27.5] days; p = 0.003), mechanical ventilation (36.5 [20–80.5] vs. 16.5 [9–25.5] days; p < 0.001), and extracorporeal membrane oxygenation (25.5 [10.75–54] vs. 10 [5–13] days; p < 0.001). Older age (> 50 years old), reason for connection different from acute respiratory distress syndrome, higher simplified acute physiology score II, diagnosis of ventilator-associated pneumonia, and infection by multidrug-resistant bacteria were independently associated to increased death rate.Infections (especially ventilator-associated pneumonia) during extracorporeal membrane oxygenation therapy are common and frequently involve multidrug-resistant organisms. In addition, they have a negative impact on patients’ outcomes.