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Summary The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n‐LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003–2013) undergoing n‐LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow‐up 2.56 years; IQR 1.01–4.65). Fifty‐three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person‐time incidence rates of Aspergillus spp. colonization and infection decreased (2003–2008, 0.19; 2009–2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003–2008, 38.1% vs 2009–2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28–41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long‐term administration of prophylaxis with n‐LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.

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