In this retrospective study we evaluated the impact of amphotericin B (AmB) deoxycholate inhalation prophylaxis on invasive aspergillosis (IA) in 611 allogeneic stem cell transplant (alloSCT) recipients and their tolerance of the inhalations. The inhalations were not used in 1996-2000 (Period I). In 2001-2005 (Period II) all patients with acute graft-versus-host disease treated with high-dose methylprednisolone used the inhalation prophylaxis with a dose of 25 mg daily. No systemic antifungal prophylaxis was routinely used during the study period. IA was detected in 17 (13 proven, 4 probable) out of 257 (6.6%) patients transplanted in Period I and in 9 (6 proven, 3 probable) out of 354 (2.5%) patients transplanted in Period II (P=0.007). The median time to the diagnosis of IA was 95 days and 155 days post transplant in the 2 periods (P=0.225). The mortality of the patients with IA was 94.1% and 66.6% in Period I and Period II. The median duration of AmB inhalation prophylaxis was 84 days. Breakthrough IA was detected in 1 of the 111 (1%) patients during the prophylaxis. No discontinuation of prophylaxis due to side effects was recorded. Overall, with a median follow-up of 3.5 and 4.6 years, 42.4% and 59% of the patients were alive in Period I and Period II, respectively (P=0.001). In conclusion, the incidence of IA fell during the AmB inhalation prophylaxis, and the inhalations were well tolerated. Mortality of patients with IA was high. The overall survival of patients was significantly higher in Period II, indicating the advances made in SCT therapy over the 10-year period.