Little data exist on the type of infections patients acquire during extracorporeal life support. Through a retrospective analysis of 109 patients who underwent 115 episodes of venoarterial extracorporeal life support, it was determined that nosocomial infections developed in 18 patients (16%). Patients with nosocomial infections were supported for longer periods of time (230 versus 140 hours; P < .05) and were more likely to have an open chest (P = .02) than those who did not have infectious complications. Blood-borne infections occurred most often while patients were cannulated for extracorporeal life support, with urinary tract and wound infections more commonly occurring after decannulation. Fungal organisms were isolated in 50% of nosocomial infections. Patients with blood or wound fungal infections had a higher case-fatality rate than those patients with bacterial complications (P = .03). Because it is unlikely that the duration of extracorporeal life support can be shortened significantly, the authors recommend an increased level of awareness of nosocomial infections in patients on prolonged extracorporeal life support. Further research is needed to assess the effects of antifungal prophylaxis or immune modulation to prevent nosocomial infections.