To investigate the frequency and costs of pulmonary exacerbations (PEx) and the association between FEV1 and PEx in patients (pts) with cystic fibrosis (CF). Chart data were linked to claims from pts with CF aged f 6 y enrolled for f 18 months in a US commercial health plan, identified between July 2008 and May 2013. The most recent 12 months (follow-up) were used to calculate outcomes. PEx were defined as f 1 of: inpatient (IP) stay coded ICD-9-CM 277.02; IP staywith ICD-9-CM for respiratory infection; new IV or oral antibiotics administered IP or outpatient (chronic use antibiotics were excluded). New PEx required a preceding f 7 days with no claims meeting PEx criteria. The best % predicted FEV 1 (ppFEV 1 ) recorded in charts during the 6 months prior to the follow-up period (baseline) was used to categorize lung dysfunction as severe (<40), moderate (40–<70), and mild (f 70). 268 pts were included (mean age 24.0 y). 88.1% of pts had f 1 PEx; 48.1% had f 1 PEx treated with IV antibiotics and/or IP stay (overall rate 2.9/y and 0.87/y, respectively). For any PEx, the mean cost was $13.1K and duration was 21 days; for a PEx requiring IV and/or IP stay, it was $36.6K and 27 days, respectively; 69% of these required an IP stay, with mean cost $47.1K. Of n = 241 pts with baseline ppFEV 1 , 71.8% were mild, 23.2% moderate, and 5.0% severe. A higher percentage of pts with moderate and severe lung disease had ≥1 PEx and ≥1 IV/IP PEx, and incurred higher unadjusted mean annual PEx costs (severe: $119.9K; moderate: $40.8K; mild: $30.1K; P< 0.001). The majority of CF pts experience ≥1 PEx/y; frequency and costs of PEx increase in pts with lower ppFEV 1 .