BACKGROUND: Few data are available on the outcome of neonatal sepsis evaluations in an era when intrapartum antibiotic therapy is common. METHODS: We identified all newborns weighing >/=2000 g at birth who were ever evaluated for suspected bacterial infection at 6 Kaiser Permanente hospitals between October 1995 and November 1996, reviewed their records and laboratory data, and tracked them to 1 week after discharge. We analyzed the relationship between key predictors and the presence of neonatal bacterial infection. RESULTS: Among 18 299 newborns >/=2000 g without major congenital anomalies, 2785 (15.2%) were evaluated for sepsis with a complete blood count and/or blood culture. A total of 62 (2.2%) met criteria for proven, probable, or possible bacterial infection: 22 (.8%) had positive cultures and 40 (1.4%) had clinical evidence of bacterial infection. We tracked all but 10 infants (.4%) to 7 days postdischarge. There were 67 rehospitalizations (2.4%; 2 for group B streptococcus bacteremia). Among 1568 infants who did not receive intrapartum antibiotics, initial asymptomatic status was associated with decreased risk of infection (adjusted odds ratio [AOR]:.26; 95% confidence interval [CI]:.11-.63), while chorioamnionitis (AOR: 2. 40; 95% CI: 1.15-5.00), low absolute neutrophil count (AOR: 2.84; 95% CI: 1.50-5.38), and meconium-stained amniotic fluid (AOR: 2.23; 95% CI: 1.18-4.21) were associated with increased risk. Results were similar among 1217 infants who were treated, except that maternal chorioamnionitis was not significantly associated with neonatal infection. CONCLUSIONS: The risk of bacterial infection in asymptomatic newborns is low. Evidence-based observation and treatment protocols could be defined based on a limited set of predictors: maternal fever, chorioamnionitis, initial neonatal examination, and absolute neutrophil count. Many missed opportunities for treating mothers and infants exist.