Background: Musculoskeletal problems are reported in the literature as a common problem for people with cystic fibrosis, with a range of aetiologies including an inflammatory arthritis. However, accurate data on the presentations and prevalence are lacking. The aim of this cohort study was to describe the scale and impact of musculoskeletal symptoms in CF. Methods: A collaboratively designed questionnaire was administered to adults attending two large UK CF centres. Data collected evaluated scale and impact of musculoskeletal symptoms. Results: Results were obtained from 489 patients (response rate 59%). Of these, 49% reported that musculoskeletal symptoms impacted their activities of daily living in the previous year. Back pain was common, occurring in 44% of participants in the preceding week. The knee was the most commonly affected painful peripheral joint, with 26% of participants reporting knee pain within the last week rising to 50% within the last year. Early morning stiffness and joint swelling were markedly less common, suggesting that the majority of musculoskeletal pain in CF is not due to an inflammatory arthritis but is due to other factors. Conclusion: Musculoskeletal problems are common in CF and frequently affect activities of daily living. Symptoms of inflammatory arthritis occurred in only a small minority of individuals. A focused approach to characterising and clarifying the aetiology of musculoskeletal symptoms is needed to inform the management of these disabling symptoms.