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Objectives: To determine the incidence, predisposing factors,clinical features, bacteriological pattern and antibiotic sensitivity in septicaemia in high-risk newborns. Design: A prospective study. Setting: Neonatal unit, Ife State Hospital, a unit of the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Nigeria. Subjects: All newborns admitted with clinical features and/or risk factors suggestive of neonatal septicaemia from February 1994 to March 1995. Main outcome measures: Culture results and mortality rates. Results: The incidence of neonatal septicaemia among new born was 22.9 per 1000 livebirths. The predisposing perinatal factors were low socio-economic status, lack of antenatal care, maternal peripartum pyrexia and congenital malformations. Gram-positive bacteria were found to be the most prevalent causative organisms (59.4%). Staphylococcusaureus (36.2%), Pseudomonas aerugirzosa (18.8%) and Coagulase negative Staphylococcus (15.9%) were the commonest causes of septicaemia. Meningitis and UTI were associated diagnoses in 16.7% and 18.2% of the septicaemic babies, respectively. The bacterial isolates showed a high degree of in-vitro antimicrobial resistance. However, all the isolates were sensitive to ofloxacin. Amongst the commonly used antibiotics, gentamicin had the lowest resistance. The overall mortality rate was 33.3%. Conclusion: Improvement in the socio-economic status of the populace and availability of affordable antenatal care would reduce the incidence of neonatal septicaemia in Nigeria. Continuous surveillance in every unit, as well as close attention to preventive strategies would be necessary to reduce morbidity and mortality from neonatal septicaemia. We recommend the inclusion of gentamicin in the initial treatment of septicaemia in the neonatal unit of OAUTHC, Ile-Ife, Nigeria.