BACKGROUND: Antibiotic therapy is essential for the treatment of cystic fibrosis (CF) lung infections. CF-specific airway pathophysiology and frequent antimicrobial exposure increase the risk of resistant infections, creating challenges to antibiotic selection. Antibiotic selection is generally based on previous cultures or hospital-wide antibiograms (HWA); however, most HWA exclude CF isolates. We developed a multi-year CF antibiogram (CFA) to compare with HWA and inform antibiotic selection. METHODS: CF culture data were collected 2015 - 2019 at a single pediatric CF center. All sputum and oropharyngeal swab isolates are included in the CFA. Demographics, microorganism isolates, and susceptibility information are presented. Susceptibilities were reported for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), Achromobacter species, Burkholderia species and Stenotrophomonas maltophilia. RESULTS: Over five years, the proportion of all SA isolates having methicillin-resistance was higher in the HWA (32%) than the CFA (28%). The most common gram-negative CF isolate was PA. Both gram-positive and gram-negative microorganisms were less susceptible in the CFA versus the HWA. CF isolates from sputum were less susceptible than oropharyngeal. MSSA and MRSA had significantly lower clindamycin susceptibility in the CFA compared to the HWA (MSSA 71% vs 79%, p<0.0001 and MRSA 39% vs 83%, p<0.0001). For every antimicrobial tested, PA isolates were less susceptible in the CFA compared to the HWA. There did not appear to be significant changes in susceptibility of CF isolates over time. CONCLUSIONS: These findings have clinical implications for empiric antimicrobial selection. A CFA will allow monitoring of resistance over time.