Background: While there has been substantial analysis of social media content deemed to spread misinformation about electronic nicotine delivery systems use, the strategic use of misinformation accusations to undermine opposing views has received limited attention. Objective: This study aims to fill this gap by analyzing how social media users discuss the topic of misinformation related to electronic nicotine delivery systems, notably vaping products. Additionally, this study identifies and analyzes the actors commonly blamed for spreading such misinformation and how these claims support both the provaping and antivaping narratives. Methods: Using Twitter’s (subsequently rebranded as X) academic application programming interface, we collected tweets referencing #vape and #vaping and keywords associated with fake news and misinformation. This study uses systematic content analysis to analyze the tweets and identify common themes and actors who discuss or possibly spread misinformation. Results: This study found that provape users dominate the platform regarding discussions about misinformation about vaping, with provaping tweets being more frequent and having higher overall user engagement. The most common narrative for provape tweets surrounds the conversation of vaping being perceived as safe. On the other hand, the most common topic from the antivape narrative is that vaping is indeed harmful. This study also points to a general distrust in authority figures, with news outlets, public health authorities, and political actors regularly accused of spreading misinformation, with both placing blame. However, specific actors differ depending on their positionalities. The vast number of accusations from provaping advocates is found to shape what is considered misinformation and works to silence other narratives. Additionally, allegations against reliable and proven sources, such as public health authorities, work to discredit assessments about the health impacts, which is detrimental to public health overall for both provaping and antivaping advocates. Conclusions: We conclude that the spread of misinformation and the accusations of misinformation dissemination using terms such as “fact check,” “misinformation,” “fake news,” and “disinformation” have become weaponized and co-opted by provaping actors to delegitimize criticisms about vaping and to increase confusion about the potential health risks. The study discusses the mixed types of impact of vaping on public health for both smokers and nonsmokers. Additionally, we discuss the implications for effective health education and communication about vaping and how misinformation claims can affect evidence-based discourse on Twitter as well as informed vaping decisions.