A total of 9,446 blood cultures were collected from adult patients at three university-affiliated hospitals. Of these, 8,943 cultures were received with both aerobic bottles filled adequately; 885 yielded 1,016 microorganisms, including 622 isolates (61%) that were the cause of sepsis, 337 isolates (33%) that were contaminants, and 57 isolates (6%) that were indeterminate as the cause of sepsis. With the exception of Staphylococcus aureus, which was recovered more often from VITAL aerobic bottles, more pathogenic microorganisms were recovered from BACTEC NR6 (aerobic) bottles than from VITAL aerobic bottles. Growth of pathogenic microorganisms was detected earlier in VITAL aerobic bottles. A total of 8,647 blood cultures were received with both anaerobic bottles filled adequately; 655 yielded 740 microorganisms, including 486 isolates (66%) that were the cause of sepsis, 215 isolates (29%) that were contaminants, and 39 isolates (6%) that were indeterminate as the cause of sepsis. More pathogenic microorganisms were recovered from VITAL anaerobic bottles than from BACTEC NR7 (anaerobic) bottles. Growth of pathogenic microorganisms was detected earlier in VITAL anaerobic bottles. In 8,500 sets all four bottles were received adequately filled. When paired aerobic and anaerobic bottle sets (systems) were compared, more pathogenic microorganisms (again with the exception of S. aureus) were recovered from the BACTEC system. For the 304 septic episodes (253 unimicrobial and 51 polymicrobial), significantly more were detected by the BACTEC system. We conclude that VITAL requires modification to improve recovery of pathogenic microorganisms to make it competitive with other commercially available blood culture systems.