Coagulase-negative staphylococci (CoNS) are the most common microorganisms isolated from blood cultures in childern, and determining whether there is true bacteremia or merely contamination is a clinical dilemma. A total of 67 episodes of CoNS-positive blood cultures in pediatric and neonatal intensive care units were evaluated during a 3-year period in order to find the possible risk factors involved and the antimicrobial susceptibility of CoNS isolates. In this study, 37 episodes were judged to be infections as opposed to 30 that were not. In comparison with individuals without infection, patients with true infection of CoNS stayed longer in the hospital (32 +/- 32.9 vs 10.7 +/- 9.3 days, p = 0.001), had more surgical procedures (32.4% vs 6.7%, p = 0.014), received more antibiotic treatments in the recent 2 weeks (37.8% vs 0%, p < 0.001), underwent more central venous catheter insertions (86.4% vs 10%, p < 0.001), received more parenteral nutrition (37.8% vs 3.3%, p = 0.001), had higher C-reactive protein profiles (4.8 +/- 5.4 vs 0.6 +/- 0.9 mg/dL, p < 0.001), and had higher neutrophil proportion (58.1% vs 44.3%, p = 0.001). However, there were no significant differences in corticosteroid therapy, hemoglobin level, total leukocyte count, and platelet count. All strains of the infection group were resistant to cefazolin, cefotaxime, penicillin, and erythromycin. Nonetheless, all isolates were susceptible to vancomycin. The percentage of multiple-resistant CoNS in the infection group was 96.9%. Empirical therapy with vancomycin for CoNS bacteremia in critically ill children is therefore recommended.