Profylactic treatment with ivIgG to preterm infants is a controvesial issue. In a prospective, randomized, placebo-controlled, multi-center study we evaluated the efficacy in preventing neonatal infections by ivIgG(Endobulin®, Immuno) profylaxis to preterm infants (gest.age <33 weeks) with umbilical cord blood IgG ≤4g/L. IvIgG or placebo(Albumin) 1g/kg body weight was given on days 0, 3, 7, 14, and 21. Eighty-one infants [ivIgG group, n=40, mean(SD) gest.age 27.5(2.2) weeks and b.w. 1.06(0.39) kg; placebo group, n=41, mean(SD) gest.age 27.7(2.5) weeks and b.w. 1.13(0.38) kg] with umbilical cord blood IgG ≤4g/L were included in the profylactic treatment study. Infants with umbilical cord blood IgG >4g/L (n=238) were not included in the treatment study but served as a separate control group. Neonatal infections according to ESPID (European Society of Pediatric Infectious Diseases) criteria and mortality were monitored until 28 days of life. The ivIgG treated infants significantly increased their serum IgG concentration during the study period compared to the placebo treated group. Infants with IgG ≤4g/L at birth showed no significant reduction in infectious episodes or mortality whether given ivIgG treatment or placebo. However, infants with IgG>4g/L at birth had significantly less infectious episodes (culture proven sepsis) than infants with low serum IgG(≤4g/L) when compared by the same gestational week (26 to 31), and had lower mortality (gest.week 26 to 27,p=0.06). We speculate that high serum IgG at birth is one indicator of a competent (mature) immune system capable of protecting the preterm infant against severe neonatal infections. This study could not prove that profylactic immunotherapy with ivIgG improves immune competence in preterm infants with low serum IgG at birth.