Abstract Background Vaccination misinformation is associated with serious public health consequences, such as a decrease in vaccination rates and a risk of disease outbreaks. Although social media offers organisations promoting vaccination unparalleled opportunities to promote evidence and counterbalance misinformation, we know relatively little about their internal workings. The aim of this paper is to explore the strategies, perspectives and experiences of communicators working within such organisations as they promote vaccination and respond to misinformation on social media. Methods Using qualitative methods, we purposively sampled 21 participants responsible for routine social media activity and strategy from Australian organisations actively promoting vaccination on social media, including government health departments, local health services, advocacy groups, professional associations and technical/scientific organisations. We conducted semi-structured, in-depth interviews to explore their perspectives and practices. Applying Risk Communication principles as a lens, we used Framework Analysis to explore the data both inductively and deductively. Results Organisations promoting vaccination face multiple challenges on social media, including misinformation, anti-science sentiment, a complex vaccination narrative and anti-vaccine activists. They developed a range of sophisticated strategies in response, including communicating with openness in an evidence-informed way; creating safe spaces to encourage audience dialogue; fostering community partnerships; and countering misinformation with care. Conclusions We recommend that communicators consider directly countering misinformation because of the potential influence on their silent audience, i.e. those observing but not openly commenting, liking or sharing posts. Refutations should be straightforward, succinct and avoid emphasizing misinformation. Communicators should consider pairing scientific evidence with stories that speak to audience beliefs and values. Finally, organisations could enhance vaccine promotion and their own credibility on social media by forming strong links with organisations sharing similar values and goals.