BACKGROUND: Cystic fibrosis (CF) patients have a high incidence of multidrug-resistant infections, rendering CF patients a treatment challenge. OBJECTIVE: To evaluate culture protocols for CF patients and develop a cost-effective culture regimen that identifies clinically relevant pathogens. STUDY DESIGN: Retrospective review. METHODS: At the time of endoscopic sinus surgery, CF patients underwent both sinus and bronchial lavage cultures. Medical records from 2002 to 2006 were reviewed. RESULTS: Twenty-four cases were identified; 12 had complete sets of cultures. Seven of 12 had sinus aerobic bacteria that were also present in bronchial culture. Anaerobic cultures from both sites were all negative (42%) or nondiagnostic (58%). Thirty-three percent of sinus fungal cultures and 91.6% of bronchial fungal cultures were positive. Sinus acid fast bacillus cultures were all negative. CONCLUSION: CF culture protocols may be streamlined by eliminating all anaerobic cultures, as well as sinus acid fast bacillus and fungal cultures for a 52% reduction in cost.