Diagnostic of early-onset neonatal infection (EONI) remains an emergency. Recent studies underline the potential benefit of using Procalcitonin (PCT) in early diagnosis of bacterial infections in neonates. The aim of this study was to evaluate the diagnostic value of an umbilical blood cord PCT based algorithm in newborns suspected of EONI. The diagnostic value of the PCT based algorithm was compared to the French one currently in use by analyzing an 18-months database of newborns suspected of EONI in University Hospital of Nantes from March 2011 to September 2012. Among the 2,408 (40.8 %) newborns suspected of infection during this period, 2,366 were included in the study. The incidence of EONI was 3.4‰ (n = 20). There was no significant difference between the sensibilities of the PCT based algorithm and the current algorithm (90 %, respectively, 95%CI 76.9-100 versus 85.4-100; p = 0.90) and between their specificities (respectively 91.7 % (90.6-92.8) versus 87.4 % (86-88.7); p = 0.25). The antibiotic treatment rate would be significantly reduced with the PCT based algorithm [211 i.e. 8.9 % (7.8-10) versus 314 i.e. 13.3 % (11.9-14.7) in the current algorithm; p < 0.005] and less biological analysis would be performed [301 i.e. 12.7 % (11.4-14) versus 937 i.e. 39.6 % (37.6-41.6); p < 0.005]. Blood cord PCT seems to be a new and efficient marker to guide neonatologists taking care of newborns suspected of EONI. The PCT algorithm seems to be a safe alternative in diagnosis of EONI, allowing detection of EONI significantly as well as the current algorithm, without resulting in a substantially higher number of missed infections. These results have to be confirmed by a multicentric validation study.