Social media offers a unique opportunity to widely disseminate HPV vaccine messaging to reach youth and parents, given the information channel has become mainstream with 330 million monthly users in the United States and 4.2 billion users worldwide. Yet, a gap remains on how to adapt evidence-based vaccine interventions for the in vivo competitive social media messaging environment and what strategies to employ to make vaccine messages go viral. Push-pull and RE-AIM dissemination frameworks guided our adaptation of a National Cancer Institute video-based HPV vaccine cancer control program, the HPV Vaccine Decision Narratives, for the social media environment. We also aimed to understand how dissemination might differ across three platforms, namely Instagram, TikTok, and Twitter, to increase reach and engagement. Centering theory and a question-answer framework guided the adaptation process of segmenting vaccine decision story videos into shorter coherent segments for social media. Twelve strategies were implemented over 4 months to build a following and disseminate the intervention. The evaluation showed that all platforms increased following, but Instagram and TikTok outperformed Twitter on impressions, followers, engagement, and reach metrics. Although TikTok increased reach the most (unique accounts that viewed content), Instagram increased followers, engagement, and impressions the most. For Instagram, the top performer, six of 12 strategies contributed to increasing reach, including the use of videos, more than 11 hashtags, COVID-19 hashtags, mentions, and follow-for-follow strategies. This observational social media study identified dissemination strategies that significantly increased the reach of vaccine messages in a real-world competitive social media messaging environment. Engagement presented greater challenges. Results inform the planning and adaptation considerations necessary for transforming public health HPV vaccine interventions for social media environments, with unique considerations depending on the platform.