The authors reviewed the charts of 26 recipients of a left ventricular assist device to determine the incidence of fungal infections and the clinical course of these patients. Nine patients (35%) had positive fungal cultures. Of these, six had clinical infections and three were colonized asymptomatically. Three of the six infected patients (including one with mediastinal sepsis and another requiring left ventricular assist device replacement for intractable fungemia) underwent orthotopic heart transplantation after successful therapy. Of the remaining three, one died of a thromboembolic stroke (probably septic in nature), one died secondary to driveline rupture, and the third succumbed to culture-negative sepsis. Two of the colonized patients underwent transplantation, and the third succumbed to perioperative right sided circulatory failure and hypoxia. Positive fungal cultures were a common finding in our series. Because of a significant incidence of fungal infection-related morbidity, the authors revised their pre operative and post operative protocol to include: 1) 2 weeks of fluconazole therapy (200 mg intravenously daily) for patients receiving broad spectrum antibiotics and for those with evidence of preoperative fungal colonization; 2) daily dressing changes around drivelines; 3) daily nystatin swish and swallow; and 4) empiric fluconazole treatment for culture-negative sepsis. Using this protocol, three left ventricular assist device recipients received prophylactic fluconazole and had no evidence of fungal morbidity or mortality on short-term follow-up.