Background: E-cigarette companies use YouTube to foster brand awareness, market their products, and interact with current and future tobacco users. However, research on the official YouTube channels of e-cigarette companies is limited. This study determined the themes of, and degree of user engagement with, videos posted to the official channels of e-cigarette companies on YouTube. Methods: Data were collected from the official YouTube channels of seven e-cigarette companies by scraping (i.e., electronically copying) the videos. The earliest video was posted on October 10, 2013, and the most recent video was posted on April 22, 2021 (n = 260). An inductive approach was used to identify themes in the data. User engagement with posts including number of likes, dislikes, and comments were also collected. Results: Prevalent themes included branding (n = 250 of 260 videos, 96%), youth use (n = 222, 85%), and tobacco use (n = 210, 81%), while less common themes included misleading health statements (n = 4, 2%), personal choice (n = 4, 2%), and antitobacco (n = 2, 1%). Videos that contained the themes testimonial, product design features, and instructional received the highest mean number of likes. Videos that contained the themes antitobacco, cessation, and testimonial received the highest mean number of dislikes. The 260 videos in this study were collectively viewed 6,619,700 times as of May 5, 2021. Conclusions: Videos from the official YouTube channels of seven e-cigarette companies often focused on branding and user experience but rarely mentioned cessation. While videos about cessation were rare, they received the second highest mean number of dislikes. Future research should assess the impact of exposure to e-cigarette-related content on YouTube and e-cigarette-related attitudes and behaviors.