The implication of highly-selective vancomycin usage on the outcome for infants with positive blood cultures for coagulase-negative staphylococci (CONS) was assessed retrospectively. The analysis was performed on partly prospective collected data from infants under 3 months of age with a least one CONS-positive blood culture in the neonatal intensive care unit at the Soroka University Medical Center between 1990 and 1996. During the study period, 239 episodes of CONS-positive blood cultures were identified from among 64,226 live births (3.7 per 1,000). Vancomycin was administered in 22 (9%) episodes, in all cases only after identification of the bacteria. The remaining 217 episodes were managed either without antibiotics or with continuation or initiation of empiric antibiotic therapy (usually ceftazidime +/- ampicillin) for suspected sepsis. Severity of the initial illness, subsequent morbidity and mortality were low regardless of the treatment administered. Only a single case of a blood-borne vancomycin resistant gram-positive organism was observed during the study period. The approach to CONS-positive blood cultures in neonates used here was associated with low morbidity and mortality. These findings support a policy of highly selective vancomycin usage in an era of emerging vancomycin resistance.