Background: Cystic fibrosis (CF) lung disease is the major cause of mortality in CF patients. Lung transplantation remains a valid therapeutic option. It is unknown whether CF patients receiving healthy lungs have an equal susceptibility to infections when compared with non-CF lung transplant patients. Herein we present the largest analyses to date of the post-operative infection profiles of 60 CF and 60 non-CF lung transplant patients. Methods: Bilateral allogeneic lung transplantations and post-transplant management were performed according to standard clinical procedures. Post-operative infections were diagnosed by conventional methods based on clinical symptoms and laboratory cultures. Results: Sixty CF lung-transplant patients developed 278 post-operative respiratory infections, from which 307 pathogens were isolated. Pseudomonas aeruginosa predominantly occupied 60.3%, followed by Mycobacteria spp (7.2%), Aspergillus spp (5.9%) and Staphylococcus spp (5.5%). However, 60 non-CF transplant patients had 154 respiratory infections with 165 pathogens isolated. Pseudomonas aeruginosa was noted in 38.2%, followed by Aspergillus spp (9.7%), Staphylococcus spp (9.7%) and Mycobacteria spp (9.1%). The CF group demonstrated a significantly higher frequency of Pseudomonas respiratory infections than the non-CF group. Interestingly, no significant differences were detected in any infections from other systems including blood, sinuses, skin, wounds, oral cavity, bowel, eyes, peritoneal cavity and urinary tract. Moreover, the CF lung transplant patients had significantly less time free from Pseudomonas infections. Conclusions: The normal lungs implanted into CF patients had significantly higher susceptibility to Pseudomonas infections than those into non-CF patients, suggesting that defective innate immunity outside the lungs contributes to CF lung pathogenesis. © 2007 International Society for Heart and Lung Transplantation.