Background: Individuals with Cystic Fibrosis (CF) tend to struggle with adherence due to complex medication regimens comprised of multiple daily dosing and various routes of administration [1]. A Medication Possession Ratio (MPR) can be calculated from refill history to provide an objective measure of overall adherence. This investigation intends to assess changes in medication adherence rates, as measured by MPR, during two distinct timeframes that encompass the introduction of Elexacaftor/Tezacaftor/Ivacaftor (ETI) use for this population. Methods: Investigators retrospectively gathered patient characteristics and fill histories for patients diagnosed with CF, on medications evaluated in the project, and seen by the adult CF team. A MPR of ? 80% was considered adherent. Data was summarized using descriptive statistics. Adherent and lessadherent patients were compared using the Chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Results: The 2022 assessment period mean composite MPR was 72% (± 23%) compared to 69% (± 25%) in 2020 (p = 0.533). Of the 89 patients in 2022 assessment period, 89% (79/89) were on a CFTR modulator compared to 85% (76) in 2020, 49% (44) were on azithromycin compared to 52% (46) in 2020, 73% (65) were on dornase alpha compared to 92% (82) in 2020, and 48% (43) were on inhaled antibiotics compared to 67% (60) in 2020. Conclusions: When using composite MPR to assess patients’ adherence to their entire treatment regimen, calculations do not reveal a statistically significant change in adherence despite less patients prescribed CF other non-modulator maintenance therapies two-years after initiating ETI