Nosocomial sepsis remains an important cause of morbidity in neonatal intensive care units. Central venous catheters (CVCs) and parenteral nutrition (TPN) are major risk factors. In-line filters in the intravenous (IV) administration sets prevent the infusion of particles, which may reduce infectious complications. We randomized infants to in-line filter (for clear fluids and lipid emulsions) or no filter placement. Sepsis, nursing time and costs were assessed. IV sets without filters were changed every 24 h, IV-sets with filters every 96 h. Of 442 infants with a CVC, 228 were randomized to filter placement, 214 to no filter. No differences were found in clinical characteristics, CVC-use, and catheter days. Nosocomial sepsis occurred in 37 (16.2%) infants with filters, in 35 (16.3%) in the group without filter (NS). Nursing time to change the IV-administration sets was 4 min shorter in the filter-group (P<0.05). Costs of materials used were comparable. In conclusion, the incidence of sepsis when using filters was not reduced but the nursing time for changing the intravenous sets was reduced without a difference in costs.