The increasing prevalence of online purchase of medications, specifically via social media platforms, poses significant health risks due to high chances of such medications being substandard and falsified (SF). The current study uses a 2 (persuasive appeal: fear vs. humor) x 3 (message repetition) mixed factorial experiment to investigate the effectiveness of persuasive appeals (on intentions to purchase medications online via social media referrals, mediated by psychological reactance (threat to freedom and anger), attitudes toward the public service announcements (PSAs), and viral behavioral intentions. ANOVA results showed the superiority of humor appeals compared to fear appeals in (1) reducing psychological reactance, (2) igniting favorable responses to the PSA, and (3) marginally reducing the intentions to purchase medications vial social media despite lower online engagement intentions (viral behavioral intentions). Pre-existing risk perceptions moderated these differences. A moderated serial mediation model, conducted using PROCESS models, was examined to assess the mechanism by which persuasive appeals and risk perceptions interact in influencing purchase intentions. Findings are discussed theoretically in regard to extending the psychological reactance model within the digital environment and practically in terms of public health, brand protection, and law enforcement recommendations.