Objective: To determine the cost effectiveness of strategies for preventing neonatal infection with group B streptococci and other bacteria in the UK and the value of further information from research. Design: Use of a decision model to compare the cost effectiveness of prenatal testing for group B streptococcal infection (by polymerase chain reaction or culture), prepartum antibiotic treatment (intravenous penicillin or oral erythromycin), and vaccination during pregnancy (not yet available) for serious bacterial infection in early infancy across 12 maternal risk groups. Model parameters were estimated using multi-parameter evidence synthesis to incorporate all relevant data inputs. Data sources: 32 systematic reviews were conducted: 14 integrated results from published studies, 24 involved analyses of primary datasets, and five included expert opinion. Main outcomes measures: Healthcare costs per quality adjusted life year (QALY) gained. Results: Current best practice (to treat only high risk women without prior testing for infection) and universal testing by culture or polymerase chain reaction were not cost effective options. Immediate extension of current best practice to treat all women with preterm and high risk term deliveries without testing (11% treated) would result in substantial net benefits. Currently, addition of culture testing for low risk term women, while treating all preterm and high risk term women, would be the most cost effective option (21% treated). If available in the future, vaccination combined with treating all preterm and high risk term women and no testing for low risk women would probably be marginally more cost effective and would limit antibiotic exposure to 11% of women. The value of information is highest (£67m) if vaccination is included as an option. Conclusions: Extension of current best practice to treat all women with preterm and high risk term deliveries is readily achievable and would be beneficial. The choice between adding culture testing for low risk women or vaccination for all should be informed by further research. Trials to evaluate vaccine efficacy should be prioritised.