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Background: With advancements in CF drug development, people with cystic fibrosis (PwCF) now take a median of seven medications daily, increasing treatment complexity, risk of drug therapy problems (DTPs), and interference with treatment goals. Given that some of these DTPs can be prevented with preemptive pharmacogenetic testing, the overall goal of this study was to test the clinical utility of a multi-gene pharmacogenetics (PGx) panel in potentially reducing DTPs in PwCF., Methods: A population based retrospective study of patients with CF was conducted at the University of Utah Health Care System. The patients were genotyped for CYP450 enzymes using a pharmacogenomic assay, and their drug utilization information was obtained retrospectively. This pharmacogenomic information was combined with clinical guidelines to predict the number of actionable PGx interventions in this patient cohort., Results: A total of 52 patients were included in this study. In the patient sample, a minimum of one order of actionable PGx medication was observed in 75 % of the cases. Results revealed that 4.2 treatment modifications per 10 patients can be enabled with the help of a PGx intervention in this patient population. Additionally, our findings suggest that polymorphisms in CYP2D6 and CYP2C19 are most likely to be the primary contributors to DTP's within PwCF., Conclusion: This study provides evidence that the PGx panel has the potential to help alleviate the clinical burden of DTPs in PwCF and can assist in informing pharmacotherapy recommendations. Future research should validate these findings and evaluate which subgroups of PwCF would most benefit from pharmacogenetic testing., Competing Interests: Declaration of competing interest Anindit Chhibber reports no potential conflict of interest. Hollyann Jacobs reports no potential conflict of interest. Alexandre Hikiji Watanabe reports no potential conflict of interest. Aditi Kharat reports no potential conflict of interest. Sakil M. Syeed reports no potential conflict of interest. Catherine M. Sherwin reports no potential conflict of interest. Nathorn Chaiyakunapruk reports no potential conflict of interest. Joseph Biskupiak reports no potential conflict of interest. Venkata K. Yellepeddi reports no potential conflict of interest. Diana Brixner reports no potential conflict of interest. David C. Young reports no potential conflict of interest., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)