Aims To determine the impact of applying the Neonatal Early Onset Sepsis Calculator (NEOSC) to clinical practice. We evaluated this multivariable risk prediction model, used in the assessment of infants >35 weeks GA, at risk of neonatal sepsis. Methods A retrospective, cohort study comparing the rates of blood culture use in a large maternity hospital before and after the introduction of the NEOSC. Cases were ascertained from the records of the Department of Microbiology. The key variables were the number of blood cultures (all gestational ages, <72 hours old), infant antibiotic use and sepsis rates. Data for three years prior to NEOSC use (January 2015 - December 2017) were compared with 15 months (January 2018 - Q1 2019) after it was implemented. Results Pre- and post- NEOSC use, the total blood cultures taken annually were: 1,312 (2015), 1,149 (2016), 1,319 (2017) and 702 (2018), 192 (Q1 2019) respectively, a statistically significant reduction [p < 0.00001, 95% CI]. There was no significant difference in rates of either: culture-confirmed GBS-sepsis [p value 0.18, 95% CI] or other-pathogen sepsis [p value 0.32, 95%CI] in term infants between the two periods. There was a significant reduction in antibiotic use in the first 24 hours of life (average 11.3% pre-NEOSC and 5.9% after NEOSC was implemented) [p < 0.00001, 95% CI]. Conclusion The introduction of the NEOSC has reduced blood culture and antibiotic use. This has been achieved without any increase in infection rates.