Burkholderia gladioli has been reported as colonizing the airways of patients with cystic fibrosis (CF) but has not previously been associated with adverse outcome. We describe six patients with CF in whom the same strain of B. gladioli, on the basis of ribotyping and biochemical characteristics, was grown in their sputum. Acquisition of this organism was followed by a fatal outcome in all six patients; one had a rapid decline in respiratory status and another developed fulminant B. gladioli bacteremia. Evidence suggests that patient-to-patient transmission of the organism occurred, and supports nosocomial infection in the ward and/or outpatient clinic despite general and stringent infection-control measures. This is the first report of adverse clinical outcome following sputum colonization with B. gladioli, and the first to demonstrate person-to-person transmission.