Abstract Background: The insertion of a long line can be a dreaded aspect of receiving courses of intravenous antibiotics for respiratory exacerbations associated with cystic fibrosis. Our study evaluates the use of ultrasound guidance in a pilot scheme to improve the experience of line insertion. Methods: Fifty-five patients commencing intravenous antibiotics for respiratory exacerbation had a long line inserted using conventional Seldinger technique, whereas 18 patients had a line inserted after the introduction of ultrasound guidance. Patients completed a questionnaire to score their satisfaction with line placement and longevity. Complication rates of the lines inserted were recorded prospectively. Results: No significant difference was found in satisfaction with line placement, line longevity, or number of attempts required to insert the line. Qualitative assessment suggests that patients preferred the use of ultrasound. Conclusions: Our study shows that routine ultrasound guidance is not associated with improvement in clinical variables, but it does have a role in the management of cystic fibrosis in adult patients.