Aim To identify the barriers and facilitators to seasonal influenza vaccination uptake among nurses.Background Seasonal influenza causes significant mortality and morbidity among older people and high-risk groups. Vaccinating nurses against influenza is an essential public health measure to reduce the burden of disease. Yet despite annual recommendations, nurses' influenza vaccine uptake rates remain low.Design An explanatory sequential mixed methods study design.Data Sources Qualified nurses attending mandatory training in two large acute hospitals in Ireland.Methods A paper-based questionnaire assessing nurses' knowledge, risk perception, health beliefs and influenza vaccination practices was distributed to a convenience sample of qualified nurses (N = 462) between September 2017 - February 2018. A self-selected sample of 35 nurses who completed the questionnaire participated in five focus groups to explore in depth the barriers and facilitating factors associated with their vaccination practices between September 2018 - October 2018. The questionnaire data were analysed statistically and thematic analysis was applied to the qualitative data. The quantitative and qualitative findings were integrated using the Pillar Integration Process.Results Seven themes emerged: (a) the influence of nurses' knowledge on vaccine uptake; (b) dissemination of information; (c) vaccine fears and concerns; (d) protection, risk and vulnerability: self and others; (e) influencers; (f) accessibility; and (g) organizational pressure.Conclusion Achieving high vaccine uptake rates among nurses through voluntary vaccination programmes remains a challenge. Multi-faceted influenza campaigns based on the HBM should be prioritized to address dissemination of evidence-based knowledge, accessibility, and external cues to action.Impact Low influenza vaccine uptake among nurses compromises patient safety and contributes to a significant burden on health services. This study identified factors associated with vaccine practices among nurses and will inform the development of specific tailored interventions for nurses.