The current study examined e-cigarette users' risk information avoidance (i.e., RIA), which is a significant challenge to e-cigarette risk communication. Applying and extending previous RIA studies and the risk information seeking and processing (RISP) model, this study identified the predictors of e-cigarette users' RIA with a comprehensive model that incorporated new roles for scientific uncertainty and relevant channel beliefs. Responses collected from an online survey were analyzed (N = 593) and support was found for two pathways that explain e-cigarette users' motivation for RIA. One suggests heightened risk perceptions were associated with strong negative affective responses that include fear, anger, sadness, and guilt. These affective responses, in turn, were positively associated with RIA intentions. The second was a direct, positive association between scientific uncertainty and RIA as well as an indirect path mediated by relevant channel beliefs. More specifically, scientific uncertainty was negatively associated with quality perceptions of e-cigarette information making it more likely e-cigarette users would avoid it. Suggestions for how to prevent or mitigate these processes that result in e-cigarette users' maladaptive response of RIA are discussed.