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; that is, healthy adults, the elderly, and people with pre-existing health conditions.MethodsA randomised controlled experiment was conducted from 29 April to 7 June 2021, which coincided with the early phases of the national vaccination programme when vaccine uptake data were largely unavailable. 5784 Malaysians were randomly allocated into 14 experimental arms and 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, the elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent were modelled and we estimated the average marginal effects based on changes in the predicted probability of responding with a positive intent for each of the four outcomes.ResultsWe found that persuasive communication via several of the experimented messages improved recommendation intentions to people with pre-existing health conditions, with improvements ranging from 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 certain outcomes with messages using negative attribute frames, risky choice frames, and priming descriptive norms.ConclusionMessage frames that briefly communicate verbatim facts and stimulate rational thinking regarding vaccine safety may be ineffective at positively influencing vaccine-hesitant individuals. Messages intended to promote recommendations of novel health interventions to people with pre-existing health conditions should incorporate safety dimensions.Trial registration numberNCT05244356.