Gain-framed health messages are found to be more effective when targeting prevention behaviors. However, framing research has only minimally investigated the role of communication mode, another important factor in health communication. This study explored the role of communication mode in interaction with message framing, and the influence of two individual differences related to involvement as conditions under which gain framing can lead to health behavior change. Participants (N = 258) were exposed to either an auditory or written health message concerning fruit and vegetable intake, with either gain- or loss-framed arguments. In addition, the online experiment consisted of baseline and posttest measures, among which intention to consume sufficient fruit and vegetables. Moderating effects of perceived baseline fruit and vegetable consumption and baseline intention were assessed. A significant interaction between message framing and communication mode was observed: In case of a gain-framed message, an auditory message resulted in a higher intention than a written message. This pattern was most explicitly found among those with a lower perceived fruit and vegetable intake at baseline. Although further research is warranted in health persuasion research, the findings can possibly be used to target health interventions better at specific groups of people who behave less healthy.