BACKGROUND The Burkholderia cepacia complex is associated with colonization or disease in patients with cystic fibrosis (CF). For patients without CF, this complex is poorly understood apart from its presence in occasional point source outbreaks. OBJECTIVE To investigate risk factors for B. cepacia bacteremia in hospitalized, intensive care unit patients without CF. METHODS We identified patients with 1 or more blood cultures positive for B. cepacia between May 1, 1996, and March 31, 2002, excluding those with CF. Control patients were matched to case patients by ward, duration of hospitalization, and onset date of bacteremia. Matched analyses were used to identify risk factors for B. cepacia bacteremia. RESULTS We enrolled 40 patients with B. cepacia bacteremia into the study. No environmental or other point source for B. cepacia complex was identified, although horizontal spread was suspected. Implementation of contact precautions was effective in decreasing the incidence of B. cepacia bacteremia. We selected 119 matched controls. Age, sex, and race were similar between cases and controls. In multivariable analysis, renal failure that required dialysis, recent abdominal surgery, 2 or more bronchoscopic procedures before detection of B. cepacia bacteremia, tracheostomy, and presence of a central line before detection of B. cepacia bacteremia were independently associated with development of B. cepacia bacteremia, whereas presence of a percutaneous feeding tube was associated with a lower risk of disease. CONCLUSIONS B. cepacia complex is an important emerging group of nosocomial pathogens in patients with and patients without CF. Nosocomial spread is likely facilitated by cross-transmission, frequent pulmonary procedures, and central venous access. Infection control measures appear useful for limiting the spread of virulent, transmissible clones of B. cepacia complex.