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This guidance aims to support the safe roll-out of COVID-19 vaccination programs. 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 the document offers 10 principles to support systems thinking for vaccination programs that apply across settings. These HF/E 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).