IntroductionVaccine safety is a primary concern among vaccine hesitant individuals. We examined how seven persuasive messages with different frames, all focusing on vaccine safety, influenced Malaysians to accept the COVID-19 vaccine, and recommend it to individuals with different health and age profiles; i.e. healthy adults, elderly, and people with pre-existing health conditions.MethodsA randomized controlled experiment was conducted among 5,784 Malaysians who were randomly allocated into 14 experimental arms. They were exposed to one or two messages that promoted COVID-19 vaccination. Interventional messages were applied alone or in combination and compared against a control message. Outcome measures were assessed as intent to both take the vaccine and recommend it to healthy adults, elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent after message exposure were modeled and we estimate the average marginal effects with respect to changes in the predicted probability of selecting a positive intent for all four outcomes.ResultsThe average baseline proportion of participants with positive intents in each arm to take, and recommend the vaccine to healthy adults, elderly, and people with pre-existing health conditions was 61.6%, 84.9%, 72.7% and 51.4% respectively. We found that persuasive communication via several of the experimented messages improved recommendation intent to people with pre-existing health conditions, with improvements ranging between 4 to 8 percentage points. In contrast, none of the messages neither significantly improved vaccination intentions, nor recommendations to healthy adults and the elderly. Instead, we found evidence suggestive of backfiring among this group with messages using negative frames, risky choice frames, and priming descriptive norms.ConclusionPersuasive messages aimed at influencing vaccination decisions should incorporate a combination of factors linked to hesitancy. Messages intended to promote recommendation of novel health interventions to people with pre-existing health conditions should incorporate safety dimensions.Clinical Trials registration numberNCT05244356Key Messages1.What is already known?Persuasive messages have been shown to influence COVID-19 vaccination intentions, but evidence from Low- and Middle-income countries are limited.There are limited studies investigating the effect of persuasive messages in influencing decisions to recommend the COVID-19 vaccine, with only a single study to date which investigated effects directed at recommending the COVID-19 vaccine to a friend, but without considering the individual’s health and age profile.2.What are the new findings?Persuasive messages that focused on vaccine safety did not positively influence Malaysian adults to take the COVID-19 vaccine or recommend it to healthy adults and the elderly, while messages framed as descriptive norms, negative attribute, and risky choices, significantly backfired for some of these outcomes.Several persuasive messages focusing on vaccine safety significantly improved intent to recommend the COVID-19 vaccine to people with pre-existing health conditions.3.What do the new findings imply?Instead of only addressing safety, persuasive messages aimed at nudging vaccination should incorporate multiple behavioral determinants linked to vaccine acceptance.Persuasive messages that are intended to promote uptake of novel health interventions should incorporate safety dimensions as a form of assurance for others to recommend it to people with pre-existing health conditions, given that they may be perceived as more susceptible to hazards from adverse events.