Objective We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks’ gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. Design and setting Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). Participants All live births ≥34 weeks’ gestation between September 2020 and August 2021. Outcome measures EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age . We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. Re