Recent research on persuasion has explored the utility of incorporating alternative emotional appeals within a fear-appeal framework to achieve persuasive outcomes. The current study contributes to this growing body of research by developing and assessing a hybrid guilt-fear message to increase human papillomavirus (HPV) vaccination intentions and comparing it to a standard fear appeal. An online experiment among men and women of vaccination age (N = 407) was conducted. Results detail the paths through which people processed the hybrid and fear appeals differently, and clarify the conditions in which utilizing guilt-based messaging strategies within a fear-appeal framework can facilitate or inhibit persuasive effectiveness. Implications for future research on multiemotion intervention messages are discussed.