BACKGROUND: Despite current prevention efforts, outbreaks of healthcare-associated infections in neonatal units remain high globally, with a considerable burden of mortality and morbidity. METHODS: We searched Medline, Cochrane Library and Outbreak database to identify studies of neonatal healthcare-associated outbreaks between 2005 and 2015 that described interventions to control outbreaks. All studies were evaluated using the ORION guidance. RESULTS: Thirty studies were identified including 17 102 infants of whom 664 (3.9%) became infected. No single intervention was identified that reduced duration or mortality. Studies that introduced multiple interventions had significantly reduced case fatality ratio and outbreak duration compared to those that used basic surveillance only. Low and low-middle income countries reported the fewest interventions to control outbreaks and these studies were also associated with higher mortality than that found in middle and high income countries. CONCLUSIONS: Systematic reporting and formal evaluation of interventions used to reduce healthcare-associated neonatal infection outbreaks is key to identifying containment strategies worldwide.