Burkholderia cepacia is an aggressive pathogen that colonizes cystic fibrosis (CF) patients, causing greatly increased morbidity and mortality. It is resistant to most antibiotics, but sensitive in vitro to a novel agent, taurolidine. This has not previously been used against B. cepacia, nor given in nebulized form. We assessed the effect of nebulized taurolidine on United Kingdom epidemic (ET12) B. cepacia infection in 20 adult CF patients attending our regional adult cystic fibrosis outpatient clinic using a prospective, randomized, double-blinded placebo-controlled crossover trial. Nebulized taurolidine (4 mL 2% solution) or saline (4 mL 0.9% solution) was given twice daily. Each arm lasted 4 weeks, with a 2-week intervening washout period. Sputum B. cepacia colony counts (primary outcome measure), spirometry, and symptoms (secondary outcome measures) were assessed. Eighteen patients completed the study. There was no change in B. cepacia colony counts or spirometry, nor symptom scores. We conclude that, although taurolidine is well tolerated in nebulized form, in this study it had no in vivo anti-B. cepacia activity.