The Extended Parallel Process Model (EPPM) posits that an effective fear appeal includes both threat and efficacy components; however, research has not addressed whether there is an optimal threat-to-efficacy ratio. It is possible that varying levels of threat and efficacy in a persuasive message could yield different effects on attitudes, beliefs, and behaviors. In a laboratory experiment, women (n = 442) were exposed to human papilloma virus (HPV) prevention messages containing one of six threat-to-efficacy ratios and one of two message frames (messages emphasizing the connection between HPV and cervical cancer or HPV and genital warts). Multiple mediation analysis revealed that a 1-to-1 ratio of threat to efficacy was most effective at increasing prevention intentions, primarily because it caused more fear and risk susceptibility than other message ratios. Response efficacy significantly mediated the relationship between message framing and intentions, such that participants exposed to a genital warts message reported significantly higher intentions, and this association can be explained in part through response efficacy. Implications for future theoretical research as well as campaigns and intervention research are discussed.