The objective of this study was to examine the clinical significance of polymicrobial bacteremia involving Pseudomonas aeruginosa. Two hundred forty-eight episodes of Pseudomonas aeruginosa bacteremia, 43 of which were polymicrobic, were studied prospectively over a 6-year period. Three sets of blood cultures were obtained for each patient. Positive results for all three blood cultures were found more frequently in patients with polymicrobial infection, who were older than those with monomicrobial infection. Patients with polymicrobial bacteremia also were worse clinically and developed shock more frequently. Crude mortality was higher in patients with polymicrobial infection. A multivariate analysis revealed three variables significantly and independently associated with polymicrobial Pseudomonas aeruginosa bacteremia: higher age, poor clinical status of the patient, and positive results for all blood cultures obtained.