Very low birthweight (VLBW) infants undergoing neonatal intensive care are at risk of infection with coagulase-negative staphylococci (CONS). This study investigates the efficacy of twice daily, 1 h infusions of vancomycin (5 mg kg) in reducing CONS infection in VLBW infants receiving parenteral nutrition. Of 72 infants in the study, 37 were randomized to vancomycin and 35 to the control group. Clinical variables and mortality were similar in both groups. In the vancomycin group, 11 infants had one or more episodes of CONS bacteraemia compared with 17 in the control group. Two babies in the treatment group had more than one episode of CONS bacteraemia, compared with nine in the control group (P = 0.02). There were 13 episodes of CONS bacteraemia in the vancomycin group compared with 29 in the control group. When only positive blood-cultures associated with a rise in C-reactive protein were considered, there were six episodes of CONS bacteraemia in the vancomycin group compared with 18 in the control group. Similarly there were five infants with one or more CONS infections compared with 11 in controls and one with more than one episode compared with six in the control group (P = 0.05). Prophylaxis with intermittent low-dose vancomycin infusions may help reduce recurrent CONS bacteraemia in VLBW infants receiving parenteral nutrition.