Invasive aspergillosis occurred in 26 liver transplant recipients since 1990 at five liver transplant centers. The median time to onset was 17 days after transplantation. Twenty-seven percent of the patients had undergone retransplantation. Invasive aspergillosis occurred significantly earlier after transplantation in smokers than in nonsmokers (P=0.017). Patients with late-onset aspergillosis (occurring after posttransplant day 90) were more likely to have had prior cytomegalovirus infection than those with early-onset aspergillosis (occurring within 90 days of transplantation) (67% vs. 10%, respectively, P=0.013). Only 8% of the patients had received additional corticosteroids or OKT3, which suggests that augmented immunosuppression may not be a relevant risk factor for invasive aspergillosis in the 1990s due to less frequent use of these agents. The median serum bilirubin level of the patients was 21.8 mg/dl, 85% of the patients had renal insufficiency, and 54% were on dialysis before the onset of invasive aspergillosis, which suggest that overall severity of illness, including poorly functioning hepatic allograft and renal failure may be the major determinants of disease occurrence. Overall mortality was 92% (24/26). No difference in mortality could be shown for the patients who received amphotericin B versus liposomal amphotericin B preparations (100% vs. 89%); however, the mean time to death after the initiation of therapy was 20 days in patients who received amphotericin B and 43 days in those who received liposomal amphotericin B preparations.