This guidance aims to support the safe roll-out of COVID-19 vaccination programmes. Vaccination programmes include a number of work systems, such as manufacturing, filling and packaging for distribution, testing and approval, cold chain delivery, booking systems for vaccination appointments, local administration of the vaccine, and patient follow-up. The challenges and requirements for operating such complex programmes at speed may vary both within a country as well as between countries, but we can offer 10 principles to support systems thinking for vaccination programmes that apply across settings. These HFE principles relate to the identification and description of work systems (Identify), the improvement of work systems and processes (Improve), and the continuous learning from experience to achieve sustainable change (Adapt).