BACKGROUND Species within the Burkholderia cepacia complex (Bcc) can contaminate medications and disinfectants and cause severe pneumonia in critically ill patients or persons with cystic fibrosis. In March 2004, we investigated a hospital outbreak of Bcc possibly associated with a contaminated nasal spray. METHODS We conducted a matched case-control study, environmental sampling, and observations of infection control practices. Case patients had infection or colonization with Bcc, and control patients had sputum culture not yielding Bcc. Isolates from patients and environmental samples were compared by pulsed-field gel electrophoresis (PFGE). RESULTS Bcc was recovered from sputum in 18 patients. Compared with matched control patients (n = 18), case patients were more likely to be receiving mechanical ventilation (p = 0.01), to have been hospitalized > 6 days (p = 0.01), and to have received antimicrobial treatment within 7 days before sputum collection (p = 0.03). Bcc was cultured from opened, but not unopened, multidose albuterol bottles, a nebulizer attached to a ventilator, and opened and unopened nasal spray bottles from contaminated lots. PFGE showed that isolates from albuterol samples and from patients were indistinguishable but unrelated to the nasal spray strain. Observations revealed improper aseptic techniques during respiratory therapy procedures and inadequate nebulizer cleaning. CONCLUSIONS Despite a temporal association with use of a contaminated nasal spray, this outbreak was caused by extrinsic contamination of multidose albuterol used for nebulization treatments and lack of adherence to infection control precautions. Implementation and re-enforcement of infection control measures successfully terminated the outbreak.