This systematic review analyzed the effectiveness of key persuasive strategies – source, appeal, framing, and evidence (SAFE) – on COVID-19 vaccination intention. Quantitative studies were searched in Web of Science, Scopus, and PubMed following the PRISMA guidelines. From the 61 studies that met inclusion criteria, source and framing are the most commonly applied SAFE strategies. However, source characteristics are a more consistent influence on vaccine intentions than message framing strategies, with expert sources and general practitioners emerging as the key sources contributing to greater vaccine intentions. In addition, a range of mediators and moderators influence the process through which SAFE message strategies impact vaccine intentions. Framing effects, in particular, are moderated by political identity, source characteristics, and vaccine perceptions. Tests of mediating processes highlight how health behavior judgments (e.g. perceived vaccine benefits, risks, trust in vaccination, perceived severity) and message response/perceptions (e.g. counterarguing, perceived similarity/empathy) operate as key intervening factors between SAFE message strategies and vaccine intentions. Overall, when practitioners apply various structural approaches (narrative elements, fear appeals, framing cues) to vaccine promotion campaigns, they should be cognizant of is providing that appeal. Targeted populations may benefit most from different structural elements if they are integrated with sources that resonate with the audience.