The use of extracorporeal membrane oxygenation (ECMO) for adult patients has increased in recent years. A retrospective cohort study of adult patients undergoing ECMO was performed between 19 February 1985 and 10 October 1995 to evaluate nosocomial infections. Seventy-one evaluable patients underwent ECMO for a total of 799 days. Forty-six infections were identified in 32 (45%) of 71 patients. There were 15 bloodstream infections, 13 lower respiratory infections, 11 urinary tract infections, and 7 miscellaneous infections. The rates of bloodstream infection (18.8 cases per 1,000 ECMO days) and urinary tract infection (13.8 cases per 1,000 ECMO days) were significantly higher than those reported through the Centers for Disease Control and Prevention / National Nosocomial Infection Surveillance System (P < .0001 and P < .001, respectively). The rate of bloodstream infection increased with the duration of ECMO cannulation. This study highlights the increased risk for nosocomial infections in this patient population. Infection may not be apparent, and increased physician awareness of infection risk is imperative.