The placement of maxillary antrostomies among cystic fibrosis (CF) patients has been used as a treatment to allow localized antibiotic lavage of infected sinus passages. This procedure is increasingly recommended by lung transplantation centers as a prerequisite prior to accepting a CF patient as a candidate for transplantation. Our study attempts to define the degree of identity between sinus, endotracheal and sputum cultures from 35 patients. The samples (n = 137) were collected within two weeks of each other. An analysis of the microbiologic type, strain, and antibiotic resistance patterns was undertaken. Randomization analysis was performed and a p-value of < 0.05 was considered significant. The results indicated a high degree of correlation between sinus-sputum pairs (n = 55) and endotracheal samples (p < 0.008). This study provides evidence that there is a potential for cross-infection between sinus passages and the lower airway. The localized irrigation of CF sinus cavities post-transplantation may be warranted in an attempt to reduce bacterial counts and potential direct infection of the allograft. However, it is unlikely that this will eliminate this risk because bacterial colonization continues and the CF trachea is another source of infection.