Background: Physical activity (PA) is a well-documented and accepted adjunct therapy for the maintenance and improvement of long-term health in cystic fibrosis (CF). Although the benefits of PA for CF populations are well-established, adherence to PA programmes within this population remains low. This study aimed to investigate the factors that influence engagement in physical activity, and to explore exercise preferences, among adults with cystic fibrosis (CF). Methods: Semi-structured telephone interviews were conducted. Participants were twenty-one adults (mean age 35 years, SD ± 8) with an established diagnosis of CF, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data. Results: Four main themes emerged: barriers, motives, value of exercise-related outcomes, and exercise preferences. The main barriers included: low energy levels, time, the weather, and exercise-related confidence. Enjoyment and perceived competence underpinned autonomous motivation. Participants who self-identified as being regularly active valued personally identified exercise-related outcomes such as, accomplishment and affect regulation. Participants indicated a preference for home-based physical activity programs compared to gym- or facility-based programs. Conclusion: Interventions aimed at promoting physical activity among adults with CF should involve programs that foster autonomous motivation, enjoyable activities, personally identified outcomes, competence and that can be conducted from the home environment. Clinical implications: To increase physical activity participation among adults with CF, interventions that can be conducted from the home environment, that pay attention to the patients’ personally-valued exercise outcomes may be required.