We conducted a retrospective post hoc analysis of prospectively collected data of cancer patients with central venous catheters (CVCs) who developed bacteremia with positive quantitative blood cultures (QBCs) drawn simultaneously through peripheral vein and CVC and which grew the same microorganisms from both blood cultures. We investigated whether clinical response of bacteremia, within 24, 48, or 72 h post-CVC removal, could be diagnostic of catheter-related bloodstream infection (CRBSI) when compared with microbiologic methods. Clinical response to antimicrobial therapy within 24 h of CVC removal in a patient with bacteremia was found to be highly suggestive of CRBSI, a finding that correlated well with semiquantitative catheter cultures and differential QBCs. However, response to antimicrobial therapy at >or=48 h after CVC removal was less likely to be diagnostic of CRBSI and could reflect a response to antimicrobial therapy irrespective of the source of the bloodstream infections.