Invasive aspergillosis (IA) remains a major cause of morbidity and mortality following solid organ transplantation. To assess the incidence of IA following lung transplantation and to identify risk factors for its occurrence, we performed a case-control study involving 101 patients undergoing lung transplantation at our institution from 1990 to 1995 and reviewed the findings. Fourteen patients (14%) developed IA. The mean time from transplantation to diagnosis was 15 months. Nine patients died; the mean time to death from diagnosis was 13 days. Risk factors associated with developing IA included concomitant cytomegalovirus (CMV) pneumonia or viremia and culture isolation of Aspergillus species from a respiratory tract specimen after lung transplantation. Optimal strategies to prevent IA in lung transplant recipients remain to be determined, but prevention of aspergillus airway colonization and CMV viremia and disease after transplantation may be important targets for prophylactic interventions.