Objectives Hand hygiene is considered the most important preventive measure for healthcare-associated infections, but adherence is suboptimal. We previously undertook a Cochrane Review that demonstrated that interventions to improve adherence are moderately effective. Impact varied between organisations and sites with the same intervention and implementation approaches. This study seeks to explore these differences.

Methods A thematic synthesis was applied to the original authors’ interpretation and commentary that offered explanations of how hand hygiene interventions exerted their effects and suggested reasons why success varied. The synthesis used a published Cochrane Review followed by three-stage synthesis.

Results Twenty-one papers were reviewed: 11 randomised, 1 non-randomised and 9 interrupted time series studies. Thirteen descriptive themes were identified. They reflected a range of factors perceived to influence effectiveness. Descriptive themes were synthesised into three analytical themes: methodological explanations for failure or success (eg, Hawthorne effect) and two related themes that address issues with implementing hand hygiene interventions: successful implementation needs leadership and cooperation throughout the organisation (eg, visible managerial support) and understanding the context and aligning the intervention with it drives implementation (eg, embedding the intervention into wider patient safety initiatives).

Conclusions The analytical themes help to explain the original authors’ perceptions of the degree to which interventions were effective and suggested new directions for research: exploring ways to avoid the Hawthorne effect; exploring the impact of components of multimodal interventions; the use of theoretical frameworks for behaviour change; potential to embed interventions into wider patient safety initiatives; adaptations to demonstrate sustainability; and the development of systematic approaches to implementation. Our findings corroborate studies exploring the success or failure of other clinical interventions: context and leadership are important.