This systematic review of 54 cross-disciplinary peer-reviewed causal empirical studies helps public health officials, researchers, and healthcare professionals better comprehend the effects of fear appeals in vaccine promotional campaigns on message processing, persuasion, vaccination attitudes, and vaccination intentions. This review documents inconsistent findings across studies, which it attempts to clarify by considering differences in research designs, sample populations, and outcomes measured. In general, we find that fear appeals increase risk perceptions, message involvement, and vaccination attitudes. However, fear appeals have less influence on vaccination intentions, especially among female and general adult populations or populations from the U.S. and other Western cultures. On the other hand, the effect of fear appeals on vaccination intentions is stronger among student populations and those from China (People’s Republic of China and Hong Kong) and other non-Western cultures. Also, fear appeals are less persuasive when promoting COVID-19 vaccines and boosters than they are for other vaccines (e.g., HPV, influenza, MMR). Future research should compare fear appeal effectiveness in messages across vaccines or when combined with other executional elements, such as the endorser or type of evidence provided. Finally, future studies should explore other methodological approaches and measure underexplored message outcomes, such as vaccine uptake behavior, in more naturalistic settings.