Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective cystic fibrosis transmembrane conductance regulator modulator. It has been shown to improve lung function and decrease pulmonary exacerbations in short-term clinical trials. The effect of ETI on hospitalization and intravenous (IV) antibiotic rates is not known. We performed a single-institution, retrospective review comparing these rates before and after the initiation of ETI.Among patients taking the cystic fibrosis modulator ETI, we compared the cumulative number of days per month hospitalized and cumulative number of days per month on IV antibiotics before and after the initiation of ETI. Electronic medical records from 37 patients were reviewed from 2016 through 2020 to identify demographic data, hospitalizations, and antibiotic use. Results were then stratified by severity of lung disease.Following the initiation of ETI, there was a decline in days per month hospitalized and on IV antibiotics. The cumulative average number of days per month patients were hospitalized decreased 86% from 27 to 4 after starting ETI. The cumulative average number of days per month on IV antibiotics decreased by 80% (32.5 to 6.4). Most of these reductions occurred among patients with severe lung disease.At our institution, we saw a decline in cystic fibrosis-related hospitalizations and in the use of outpatient IV antibiotics following the initiation of ETI. These reductions were most pronounced among patients with severe lung disease.The initiation of ETI was associated with a decline in days hospitalized and days on IV antibiotics.