The rapid development of short-video social network platforms provides us with an opportunity to conduct health-related advertising and recommendation. However, so far, there are no empirical evidence on whether users are willing to accept health-related short-video advertisements. Here, acceptance refers to purchase intention, meaning that users will read short-video ads, share ads with others, or even open the product link embedded in ads to purchase the product. In this paper, we make the first attempt to model and quantify user acceptance of health-related short-video advertisements. Particularly, we propose a new research model that enhances the Technology Acceptance Model (TAM) with two new designs. First, we propose four new antecedents including social interaction, intrusiveness, informativeness, and relevance into the original TAM to reflect the features of short-video social networks. Second, we introduce two mediator variables including perceived usefulness and attitude so that we can better study how different factors affect user acceptance of health-related short-video ads. We perform a survey on the Internet and conduct an empirical analysis of the surveyed data. The results show that the four antecedents as well as the perceived ease of use have significant influences on perceived usefulness, attitude, and purchase intention. Further, perceived usefulness plays a valid mediating role in attitude and purchase intention. We also found that users’ perceived ease of use on health-related short-video ads cannot significantly predict users’ attitudes toward ads. This is a new finding in social media-oriented ads. Finally, we integrate the empirical findings and present reasonable suggestions for advertisers and marketers to promote health-related short-video ads.