Health promoting messages can be framed in terms of the gains that are associated with healthy behaviour or the losses that are associated with unhealthy behaviour In this study, we examined the influence of self-efficacy to quit smoking on the effects of gain framed and loss framed anti-smoking messages in a randomized controlled trial among 539 adult smokers. Participants with a high self-efficacy to quit smoking reported higher levels of motivation to quit smoking after receiving a loss framed message than after receiving a gain framed message or no message. For these participants receiving a gain framed message did not result in a higher motivation to quit smoking than receiving no message. For participants with a low, self-efficacy to quit smoking there were no differences in motivation to quit smoking between the gain framed message condition, loss framed message condition and control condition. Our results suggest that self-efficacy can moderate the effects of message framing on persuasion.