Injuries are the leading cause of childhood death internationally; steep social gradients exist in mortality and morbidity. The majority of pre-school injuries occur in the home, but implementing research into practice for injury prevention has received little attention. This systematic review describes key facilitators and barriers when implementing injury prevention interventions. The review used articles included in a Cochrane systematic review of the effectiveness of home safety education, with or without the provision of safety equipment. Each paper was screened to ensure that children under 5 years, intervention details and process measures and/or barriers and facilitators were included. Two authors independently reviewed each paper and extracted data. Themes were identified and framework analysis used in an iterative process. Ninety-nine papers were identified, 42 excluded and 57 included in the analysis. Seven facilitators and six barriers were identified. Facilitators related to the approach used, focused messages, minimal changes, deliverer characteristics, equipment accessibility, behaviour change and including incentives. The barriers included complex interventions, cultural, socio-economic, physical and behavioural barriers and deliverer constraints. Barriers and facilitators should be addressed when implementing injury prevention interventions and studies should explicitly explore factors that help or hinder the process.